Insulin

Insulin By pancreas In islet beta cells by endogenous or exogenous substances such as Glucose , lactose , Ribose , Arginine , Glucagon A protein hormone stimulated secretion. Insulin is the only organ blood glucose lowering hormone, while promoting Glycogen , Fat , Protein Synthesis。 Exogenous Insulin is mainly used to Diabetes Treatment。
Insulin

Insulin The discovery process

Insulin In 1921 by the Canadian F.G. Banting And C.H. Best First discovered. One
 Under the microscope of islet beta cells Under the microscope of islet beta cells
The beginning of the 922 year for clinical treatment, the past Diabetes Patients have been saved. Study on the detection of Chinese nephropathy Institute for clinical indications until the early 80s, the Insulin Almost all extracted from pig and bovine pancreas. Different animal insulin composition are different, and the structure of porcine insulin is most similar, only a B chain carboxyl terminal Amino acid Different. At the beginning of 80s has been successfully used genetic engineering techniques produced by a large number of people microbial insulin, and has been used in clinical.
In 1955 the British F. group by Sanger Bovine insulin All Amino acid Sequence, opened the humanity to know the chemical structure of the protein molecule road. In September 17, 1965, China scientists synthesized with full biological activity Crystalline bovine insulin It is the first, using protein artificial synthesis method in the laboratory, and later the United States and the Federal German scientists have completed similar work.
In early 70s, the British and Chinese scientists successfully using X ray diffraction method were determined. Porcine insulin The three-dimensional structure. These work laid the foundation for further study of the relationship between the molecular structure and function of insulin. People with chemical synthesis and preparation method of semi synthetic analogues, study the structure change influence on the biological function of different kinds of comparative study on the genus; insulin; abnormal insulin molecule disease due to insulin gene The mutation of individual amino acids in the insulin molecule produced a change Molecular disease . The research also has important practical significance to elucidate the etiology of some diabetes.
The first generation of animal insulin - insulin
1921 Frederick Badin (Frederick Banting) and John James Rickard Macleod (John Macleod) cooperation successfully for the first time to extract the insulin, different races of mammals (human, cattle, sheep, pigs and so on) of the insulin molecule Amino acid Sequence and structure is slightly different, the porcine insulin and human is most close to. Animal insulin is insulin injection was used in the treatment of diabetes, usually porcine insulin, porcine insulin and human insulin in the presence of 1 to 4 amino acids, so prone to immune response, subcutaneous fat atrophy or hypertrophy, insulin allergic reaction, and due to its high immunogenicity, easy to repeated high hyperglycemia and hypoglycemia, prone to insulin resistance.
The second generation of insulin - insulin
In 1980s, people through genetic engineering (recombinant (DNA) Transgene (yeast) beer yeast . Pichia pastoris or Hansenula polymorpha) or recombinant Chinese hamster ovary cells (Chinese CHO ) express high purity synthetic human insulin, its structure and human insulin secretion.
Comparison of animal insulin, insulin allergy or less insulin resistance So, the subcutaneous fat atrophy phenomenon is also reduced due to human insulin antibody; less so than animal insulin injection volume reduced by 30% in average; stability of human insulin than animal insulin, at room temperature 25 degrees Celsius can be stored at room temperature for human insulin for 4 weeks.
The onset time, peak time, duration of action can not simulate physiological insulin secretion pattern. In 30 minutes before a meal injection, have higher risk of nocturnal hypoglycemia.
The third generation of insulin analogues
At the end of 1990s, found in the deep research on the structure and composition of human insulin, modification of peptide chain: using gene engineering technique, change the amino acid composition of some parts of the insulin peptide change; isoelectric point; six dimer with cobalt ion substitution strength; zinc ion; increase the fatty acid chain in the molecule, increase the binding with albumin, may change its physicochemical and biological characteristics, so as to develop more suitable for human physiological need of insulin analogues (insulinsimilitude). Insulin analogues can be used next meal, also known as prandial insulin or insulin.

Insulin Variety classification

Source: the control of insulin synthesis gene In the eleventh Chromosome On the short arm. Insulin gene will generate a normal structure is normal; if the insulin structural gene mutation is generated is not normal, for the variation of insulin. In the beta cell nucleus, Eleventh DNA of insulin gene region on the short arm of chromosome mRNA transcription, mRNA from the nucleus moved to the cytoplasm of the endoplasmic reticulum, translated by 105 Amino acid residues A preproinsulin. Preproinsulin after proteolysis in the propeptide, generating 86 amino acid long peptide - proinsulin (45343345). Proinsulin with microbubbles into the cytoplasm Golgi apparatus After. Proteolytic enzyme The effect of 75, 55, 6075, cut three Arginine Connect the broken chain chain, generating no effect C peptide At the same time, insulin, secreted into beta cells, into the blood circulation. After enzymatic hydrolysis of proinsulin, a small part with insulin into the blood circulation, insulin biological activity of insulin only 5%.
Inactivated .
Islet beta cells in insulin secretion reserve of about 200U, about 40U every day. When the fasting plasma insulin concentration is 5 ~ 15 U/mL. After the meal the plasma insulin levels can increase 5 ~ 10 times.
1, animal insulin from pigs and cattle pancreas In the extraction, they are the same efficacy.
1, ultra short acting: 15 minutes after injection effect, peak concentration 1~2 hours (subcutaneous). (for example, insulin aspart insulin lispro)
2, short acting (available): 30 minutes after injection work, the peak concentration of 2~4 hours, 5~8 hours of continuous (intravenous, intramuscular, subcutaneous). (such as insulin, regular insulin)
3, the effect of injection of 2~4 hour after the onset, the peak concentration of 6~12 hours, 24~28 hours (continuous subcutaneous). (such as Protaphane)
4, long-term injection 4~6 hours after onset, high 75527 two. (protamine zinc insulin)
5, ultra long term: after injection of 3~6 hours of onset, maintenance time is 6~24 hours (subcutaneous). (insulin glargine, insulin detemir)
6, pre mixed injection 0.5 hours after onset, duration of 24 hours (subcutaneous). (biphasic insulin)

Insulin Structure

 The structure of insulin The structure of insulin
Different races (human, animal cattle, sheep and pigs) insulin function is roughly the same, slightly different composition. The figure for the Human insulin Chemical structure.
Insulin by A, B two peptide Chain composition. Human insulin (Insulin Human) A chain with 11 21 Amino acid B, there are 15 kinds of chain of 30 amino acids, A total of 16 51 amino acids Form。 The A7 (Cys) -B7 (Cys), A20 (Cys) -B19 (Cys) four cysteine In Sh Form two Two disulfide bonds So, A, B two chain link. In addition A chain A6 (Cys) and A11 (Cys) is a two disulfide bond.

Insulin secretion

Biosynthesis of insulin is affected by the velocity of the plasma glucose concentration, when the blood glucose concentration increased, the increase in the content of beta cell insulin, insulin synthesis accelerated.
In islet beta cells in insulin synthesis. The molecular weight of insulin 5700, consisting of two amino acid peptide. The A chain of 21 amino acids, B 30 amino acid chain. The A-B chain between two Two disulfide bonds To be connected。
Insulin and C peptide with the same molecule secreted into the blood. The clinical use of insulin in the treatment of patients in serum Insulin antibody Determination of serum insulin levels, effects of radio immunity method, in this case through the determination of serum C peptide level, to understand the status of endogenous insulin secretion.
influence factor
The secretion of insulin is mainly affected by the following factors:
 Stimulation of insulin secretion Stimulation of insulin secretion
The plasma glucose concentration The plasma glucose concentration is the most important factor affecting insulin secretion. Oral or intravenous glucose, insulin release in two-phase reaction. Early rapid phase, portal vein Which reached the highest value in plasma insulin in 2 minutes, then decreased rapidly; slow phase, 10 minutes after the plasma insulin levels and increased gradually, lasted more than 1 hours. Early rapid phase showed glucose insulin release to storage, slow phase showed insulin synthesis and insulin changes of insulin.
Eat more protein containing foods Eating food containing more protein, increased amino acid concentration in the blood, insulin secretion also increased. Arginine Lysine, leucine and Phenylalanine Have a strong stimulation of insulin secretion function.
After eating gastrointestinal hormone increases After eating gastrointestinal hormone increases can promote insulin secretion such as gastrin , Secretin , gastric inhibitory peptide, intestinal vascular Active peptide It stimulates insulin secretion.
Autonomic nervous system function The vagus nerve When promoting insulin secretion; Sympathetic excitement When the inhibition of insulin secretion.

Insulin insulin receptor

Insulin biological effects at the cellular level is specific receptor with the target cell membrane binding and promoter. Specific parts of the target cell membrane insulin receptor to insulin action, only with insulin or insulin containing molecules Proinsulin Combined with a high degree of specificity, and is widely distributed. The receptor is a glycoprotein, each receptor by alpha and beta two subunit composition, and by the two Subunit Poly receptor type four. The alpha subunit through the cell membrane, is exposed on the surface of cell membrane, with insulin binding sites. The beta subunit from the cell membrane to the cytoplasm is extended, insulin induces functional units of cell membrane and intracellular effect. Insulin and subunit binding, tyrosine kinase beta subunit is activated, the receptor phosphorylation, which mediated regulation of cell enzyme system activity, metabolic control. And by the two subunits of poly receptor type four. Each cell in combination with insulin depends on receptor number and affinity, the two by adjusting the concentration of plasma insulin. When the concentration of insulin increased often insulin receptor number decreased, called down regulation. Such as the obese non-insulin-dependent diabetic patients due to fat cells The number of receptors on the membrane was decreased, the clinical sensitivity of insulin resistance, said. When obese patients with non-insulin-dependent diabetes through diet and exercise after weight loss, fat cell membrane insulin receptor The number, strengthen and make blood sugar and insulin binding capacity by improving. This is not only an important pathogenesis of obese non-insulin-dependent diabetes mellitus, theoretical basis weight must be in the treatment of.

Insulin metabolize

Insulin by pancreatic beta cells by endogenous or exogenous substances such as glucose, lactose , Ribose , Arginine , Glucagon A protein hormone stimulated secretion.
The first secretion is composed of 84 amino acid long chain peptide - proinsulin (Proinsulin), the specificity protease - proinsulin invertase (PC1 and PC2) and Thabo carboxypeptidase E, the middle part of proinsulin (C chain) cut, while the carboxyl end portions of proinsulin (A chain) and the N-terminal part (B chain) together to form two disulfide bonds by insulin.
Mature insulin stored in islet beta cells in the secretory vesicles, the existence of six dimers with zinc ion coordinated way.
Under the external stimulation with insulin secretory vesicles released into the blood, and play its physiological role.
Insulin secretion is divided into two parts, a part to help maintain normal fasting blood glucose and insulin secretion, called insulin, the other part is to reduce postprandial hyperglycemia, maintain normal postprandial blood glucose and insulin secretion, called prandial insulin. In the early phase of prandial insulin secretion increased blood glucose control postprandial amplitude and duration, its main role is to inhibit the formation of liver endogenous glucose. Through this mechanism, the blood glucose at any time can be controlled in close to the fasting level; postprandial blood glucose peak below 7 mmol/L, and blood glucose levels are higher than 5.5 mmol/L no more than 30 minutes. In patients with type 1 diabetes in the diagnosis of diabetes before, most patients with pancreatic beta cell autoimmune destruction, leading to food and decreased basal insulin secretion. Type 2 diabetes pancreatic dysfunction often shows slow progress, peripheral insulin resistance, but also the first phase insulin secretion, and thus can appear normal fasting blood glucose and postprandial blood glucose. Finally, the postprandial blood glucose level can reach 4 times the physiological state of non diabetes, and elevated blood glucose after meals in the last several hours, so that in the next meal still increased significantly. Insulin make up the lack of prandial insulin secretion Novolin R, Insulin analogues Preparations Aspart Etc.. Basal insulin on islet cell 24 hours of continuous pulse type insulin secretion, is mainly used to maintain the normal fasting blood glucose levels. The American Diabetes Association (ADA) and the European Diabetes Association (EASD) guidelines suggest that in the lifestyle intervention and oral treatment of diabetes, if blood glucose control is not satisfactory, should start insulin therapy as soon as possible, and the choice of basal insulin and oral hypoglycemic drug combination. If this therapy can not control blood sugar, according to the treatment of the guide line, on the basis of recommendations at meals plus insulin. At present, to make up for the preparation of basic insulin deficiency include basal insulin analogue insulin detemir.
Insulin by insulin degrading enzyme (Insulin Degrading Enzyme, IDE Degradation). Amylin and beta amyloid polypeptide is IDE substrate .
Insulin fibrosis: through clinical medicine as well as a large number of scientific research, amyloid fibrosis and type II diabetes, insulin is closely related.

Insulin Function

Insulin pharmacological action

The treatment of diabetes, wasting disease. Promote the blood circulation of glucose into liver cells, muscle cells, fat cells and other tissue cells, glycogen synthesis can lower blood glucose, promote the synthesis of fat and protein.

Insulin Physiological function

The main physiological function of insulin is to regulate metabolism. On glucose metabolism: promote the uptake and utilization of glucose in tissues and cells, glycogen synthesis, inhibition of gluconeogenesis, lowering blood sugar; metabolism of fat: promote the synthesis of fatty acid and fat storage, reduced fat decomposition; protein: promoting amino acids into cells, promote protein synthesis links to increase protein synthesis. The total effect is to promote metabolism. Insulin is the only organ to reduce blood sugar The hormone, and only at the same time promote Glycogen Fat, protein synthesis, hormone. The mechanism belongs to Receptor tyrosine kinase Mechanism.

Insulin Regulation of glucose metabolism

Insulin can promote the uptake and utilization of glucose in the body tissue, and the inhibition of glycogen decomposition and Gluconeogenesis Therefore, have the function of reducing blood sugar, insulin. Excessive insulin secretion, blood glucose decreased rapidly, the brain can appear most affected, convulsions, coma, and even cause insulin shock . On the contrary, the lack of insulin secretion or insulin receptor Deficiency often leads to elevated blood sugar; if more than Renal glucose threshold Then, sugar from the urine, caused by diabetes; at the same time as the change in blood components (excess glucose), also cause hypertension, coronary heart disease Retinal vascular disease and other diseases. Insulin is the result of various causes:
(1) promote muscle, adipose tissue At Target cell The cell membrane carrier in blood glucose transport into the cell.
(2) enhanced through covalent modification phosphodiesterase Activity, reduce the level of cAMP, increased CGMP The concentration, so that the Glycogen synthase Increased activity, phosphorylase Decreased activity, accelerated glycogen synthesis, inhibition of glycogen decomposition.
(3) and by activation of pyruvate dehydrogenase phosphatase Pyruvate dehydrogenase Activation, acceleration Pyruvic acid Oxidation Acetyl coenzyme A Sugar, accelerate Aerobic oxidation .
(4) reduced by inhibition of PEP carboxykinase synthesis and Gluconeogenesis The raw materials, inhibition of gluconeogenesis.
(5) inhibiting hormone sensitivity of adipose tissue in lipase Slow down. Fat mobilization To use glucose, increase.

Insulin Regulation of fat metabolism

Insulin can promote fat synthesis and storage, to reduce the serum free fatty acid, inhibit fat oxidation and decomposition. Insulin deficiency can cause fat metabolism and reduce fat storage, strengthen the decomposition, elevated blood lipids, a long time can cause arteriosclerosis, leading to serious diseases of cardiovascular; at the same time, the lack of insulin leads to body fat decomposition to strengthen, generate a large number of Ketone There. ketoacidosis .
Regulation of protein metabolism
On the one hand to promote cell insulin uptake of amino acids and protein synthesis, inhibiting a protein decomposition, which is conducive to growth. Pituitary gland growth hormone Promoting protein synthesis, must have the presence of insulin can be shown. Therefore, for the growth of hormone, insulin is indispensable.

Insulin Other functions

Insulin can promote potassium ion and magnesium ions through the cell membrane into the cell can promote; Deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and adenosine triphosphate (ATP) synthesis.

Insulin Against hormone

 Glucagon Glucagon
The main body of anti insulin hormone Glucagon Adrenaline, and Norepinephrine Adrenal cortical hormone, growth hormone, etc.. They can make blood sugar rise.
(1) glucagon (glucagon). The islet Alpha cell The secretion of insulin resistance in the regulation of blood glucose concentration. The main role of glucagon glucagon is rapidly to liver glycogen decomposition, and promote hepatic glucose output,
Enter the blood circulation, to improve the level of blood glucose. Glucagon can strengthen Liver cell The intake of amino acids, and can promote lipolysis in extrahepatic tissues, increase the input of glycerol liver, provides a lot of gluconeogenesis and raw materials to strengthen gluconeogenesis. Glucagon glucagon and insulin homeostasis coordinated blood glucose levels.
Eating carbohydrates, produce large amounts of glucose stimulated insulin secretion, and at the same time, glucagon secretion was inhibited, insulin / glucagon ratio increased significantly, the change of liver glucose mainly generated from the organization for the conversion of glucose to glycogen and glycogen storage organ.
Hungry, blood glucagon levels increased significantly while the insulin level decreased. Gluconeogenesis and glycogen decomposition accelerated, liver continue to be transported to the blood glucose. At the same time due to a decrease in insulin levels, muscle and adipose tissue's ability to use glucose decreased, mainly the use of fatty acids, thereby saving glucose to ensure brain glucose supply enough.
(2) epinephrine and norepinephrine. Epinephrine is Adrenal medulla The secretion of norepinephrine secretion of sympathetic nerve endings. When stress or cold stimulation of sympathetic nerve in the excited state, adrenaline And norepinephrine secretion increased, the liver glycogen decomposition output increased, hindering the glucose into muscle and fat cells, increase blood sugar.
(3) growth hormone and growth hormone inhibiting hormone.
The growth hormone. By the anterior pituitary secretion, it can promote the growth, metabolism and can regulate the body's. Growth hormone mainly through the inhibition of muscle and adipose tissue glucose utilization, and promote the liver gluconeogenesis and glycogenolysis, so that increased blood sugar. Growth hormone can promote the decomposition of fat, plasma free fatty acids Rise。 Hunger reduced insulin secretion, growth hormone secretion increased, and blood glucose utilization and reduce fat utilization increased, the plasma levels of glucose and free fatty acid content increased.
The growth hormone inhibiting hormone. Secreted by islet D cells. The secretion of growth hormone release inhibiting hormone not only inhibits pituitary growth hormone, and inhibition of insulin and glucagon secretion under physiological conditions. But the use of growth hormone release inhibiting hormone itself on hepatic glucose production or circulating glucose had no direct effect.
(4) Adrenal gland Glucocorticoid . Glucocorticoid is by adrenal cortex Secretion (mainly cortisol That is, hydrocortisone), can promote the decomposition of liver protein, the amino acid in the liver increased, and a variety of synthesis key enzyme related induced gluconeogenesis, thus promote gluconeogenesis, increase blood sugar.
(5) the free nerve function may affect the secretion of insulin.
Promote insulin secretion vagus nerve; sympathetic nerve is the inhibition of insulin secretion. From the above that DNA to mRNA gene transcription, spanning 86 amino acid long peptide - proinsulin (Proinsulin). Proinsulin with microbubbles into the cytoplasm Golgi apparatus After. Proteolytic enzyme The effect of 31, 32, 60, cut three Arginine Connect the chain, the above results obtained!

Insulin Insulin treatment

Insulin Indication

In patients with type 1 diabetes, because their islet beta cell function impaired insulin secretion absolutely insufficient, when in the pathogenesis of insulin treatment, but also need lifelong insulin replacement therapy to maintain life and life. About the total number of 5% diabetes mellitus. Type 2 diabetes mellitus Based on lifestyle and treatment with the combination of oral hypoglycemic drugs, if the blood sugar is still not under control, combined treatment can begin oral drugs and insulin. After combined treatment of large dose of many oral drugs after HbA1c is still greater than 7%, you can consider starting insulin therapy. New onset and type 1 diabetes mellitus and diabetic patients is difficult to distinguish the thin. In the course of diabetes (including newly diagnosed patients with type 2 diabetes), appear no obvious incentive weight loss, should as soon as possible the use of insulin therapy. For high blood glucose in newly diagnosed type 2 diabetic patients, the oral drug is difficult to obtain satisfactory control of blood glucose, and high blood glucose toxicity can rapidly relieve part to reduce insulin resistance and reverse beta cell function, so the newly diagnosed patients with type 2 diabetes and hyperglycemia when using intensive insulin therapy. There are some special cases to insulin therapy: Perioperative period Serious complications or acute; Stress state When the temporary use of insulin through the dangerous period, such as diabetic ketoacidosis, hyperosmolar hyperglycemia, lactic acidosis, infection; severe chronic complications, such as diabetic foot and severe diabetic nephropathy; some serious diseases, such as coronary heart disease, Cerebral vascular disease , Blood disease Liver disease, etc.; Gestational diabetes mellitus And the diabetic pregnant women, gestation Period, childbirth Before and after lactation, such as blood sugar can not be used to meet the requirements of the diet control target, need to be treated with insulin, disable oral hypoglycemic drugs. Secondary diabetes mellitus And the specificity of diabetic patients.

Insulin Insulin preparation

According to the sources of insulin and chemical structure can be divided into: animal insulin, insulin, insulin
Analogue. People such as insulin Novolin series, Insulin analogues Such as novorapid, novorapid 30, Nobel peace. According to the characteristics of time can be divided into: insulin aspart, Short acting insulin In effect, insulin and long-acting insulin (including long-acting insulin analogues) and premixed insulin (premixed insulin analogues), common insulin analogues such as insulin aspart, long-acting insulin analogues such as Nobel peace. Clinical trials demonstrated that insulin analogues secretion and decrease in simulated physiological insulin Hypoglycemia The risk of occurrence than that of human insulin.
According to the classification of insulin efficacy length:
1, ultra short acting: 15 minutes after injection effect, peak concentration 1~2 hours.
2, short acting (available): 30 minutes after injection work, the peak concentration of 2~4 hours, 5~8 hours continuously.
4, long-term (protamine zinc insulin injection): 4~6 hours after onset, the peak concentration of 4~20 hours, 24~36 hours continuously.
5, pre mixed: the short effect and the effect of pre mixed, a shot, and the rapid onset (30 minutes), lasted for 16~20 hours.
The common market has 30% short acting and 70% effect of premixed and short, in effect, accounting for 50% of the pre mixed two.

Insulin Use note

Begin insulin therapy should continue to adhere to the diet and exercise, and for patients to strengthen the education, encourage and guide patients to self monitoring of blood glucose, to facilitate insulin dose adjustment and prevention of hypoglycemia. At the beginning of all insulin treated patients should accept the hypoglycemia risk factors, symptoms and self-help measures of education.
Treatment of insulin should simulate physiological insulin secretion pattern, including Basal insulin and Prandial insulin The two part of the supplement. Scheme selection should be highly individualized, according to blood glucose for step therapy driven, as soon as possible to control blood glucose stable.
Learn to self observation often use finger to press the injection parts have no induration, pain, severe should consult medical professionals, injections to avoid these parts. Injection of insulin, should bring Blood glucose meter That day, self testing blood glucose, blood glucose fluctuation will understand each time, record the results for review when doctors adjust the dose of insulin.
The adverse reaction of excessive injection
If in the treatment of insulin overdose, will cause the hypoglycemia, lesser poisoning, mainly affect the autonomic nervous system, as hunger, dizziness, pale, weak and sweating, also can have the tremor, precordial discomfort, facial and limb numbness, headache. When blood sugar is further reduced, affecting the central nervous system, appear dysphonia, diplopia, muscle tremors, ataxia, and delirium and degree of seizures, this state is called insulin shock, if not timely rescue can cause death.

Insulin The injection site notice

Insulin is a technology for diabetes patients should master". In addition to the injection, site selection is also very important, because the injection site right can not only reduce the injection risk, also contribute to the absorption of insulin.
The abdomen is: should be preferred site because of subcutaneous abdominal fat thickness, can reduce the risk of injection to the muscle layer, pinch abdominal skin most easily, is also the fastest part of the absorption of insulin. Should be in Navel Both sides by 3 ~ 4 refers to the distance to the sides of the body subcutaneous injection, the layer is thin, the more easily tied to the muscle layer. This site is the most suitable for injection Short acting insulin Or with the effect of mixed collocation of insulin.
In addition, the lateral thigh and buttocks, upper arm lateral part 1/4 is also suitable for insulin injection site.
Thigh: only by the front or side of the thigh medial injection, blood and nerve distribution more, should not be injected. The injection must pinch thigh skin or using superfine chaoduanxing (5 mm) pen needles.
The 1/4 part: the lateral arm is the most suitable for self injection parts, because the subcutaneous tissue of upper arm is thin, easy injection to the muscle layer: self injection to pinch the skin. We must recommend the use of injection arm, superfine chaoduanxing pen needles (5 mm) or by the medical staff and family assistance injection.
Hip: hip for injection, long-acting insulin (such as bedtime NPH insulin injection), because the subcutaneous layer of hip is thick, the absorption of insulin is slow, so can very good control of fasting blood glucose, and need not knead the skin or muscle injection risk.

Insulin Storage method

Insulin should be stored in refrigerator below 10 DEG C, can maintain the activity of 2~3 in the refrigerator constant temperature of 2 DEG ~8 DEG, even partially suction using insulin. When in use, the temperature no higher than 30 and less than 2 DEG C place can, but must avoid the sun, in case of failure.
Is in the use of insulin, as long as on the indoor shade on it. Open a bottle of bottled in the use of insulin can be placed in the refrigerator freezer, saving about 3 months. The use of insulin and insulin pen refills do not put together back in the fridge, portable storage for 4 weeks.
If it was cloudy insulin for several hours or may jolt is not properly preserved when will form a mass, then the insulin should be discarded.
1, insulin due to avoid heat and direct sunlight.
2, insulin should be kept in the refrigerator 2--8 C, unopened insulin should be used in shelf life.
3, open the insulin placed in the refrigerator shelf life of January, marked the opening time.
4, don't take insulin placed in the refrigerator freezer layer, frozen insulin can not be used, only in the cold room.
Remove from the refrigerator 5, insulin injection before placement after 20 minutes after the injection at room temperature.
6, the installation of insulin injection pen refill, please don't be kept in the refrigerator can be placed in the shade.
7, air travel should be insulin carry, do not put in the sustenance of the luggage.

Insulin Insulin response

Insulin Systemic reactions

The most common hypoglycemia. In severe or brittle type I and II type, especially thin. The general activity is too much, too little, or even diet reduction, blind or excessive doses. The symptoms of hunger, dizziness, weakness, sweating, palpitations, even neurological symptoms, such as directional disorders, irritability, and incoherent cry laugh fugacious, sometimes even more serious. Faint , Twitch And like epilepsy, In So, death. The church should be familiar with the patient response and be vigilant the course of treatment, early feeding or sugar confectionery confectionery to alleviate the severe, should immediately intravenous injection of 50% glucose above 40ml, followed by intravenous infusion of 10% dextrose in water until awake; sometimes the first note Glucagon Every time, subcutaneous or intramuscular 1mg, such as Hypoglycemia The reaction lasted a long seriousstill can use hydrocortisone, every 100 ~ 300mg to 5% ~ 10% glucose intravenous drip of water. When hypoglycemia after recovery must be carefully estimated the next dose, analysis of the disease, to prevent recurrence. In the times of hypoglycemia due to stimulation of islet alpha cells and Adrenal gland Can react with hyperglycemia (Somogyi effect), which often leads to brittle type, must be avoided.
The allergic reaction: a minority of patients with allergic reactions, such as Urticaria , Angioedema , Purpura There are very few. Anaphylactic shock . This reaction due to impurities in the preparation by roughly. Light cure with anti histamine drugs, or shall be the replacement of high purity agents such as Actrapid, because of its Amino acid With the same sequence of endogenous insulin, and contains impurities, cause allergy is extremely rare, or can use oral medicine. When necessary can also use the small dosage insulin subcutaneous injection of Yi desensitization treatment.
The insulin edema: diabetes without control often before the water loss of sodium, glucose control cells decreased after 4 ~ 6 days can occur in water and sodium retention and edema, and insulin may promote renal tubular reabsorption of sodium, known as insulin edema .
The insulin treatment: refractive arrhythmia patients sometimes sense Blurred vision The treatment, blood glucose decreased rapidly and the effects of osmotic pressure of lens and vitreous, the crystalline body water escape and refraction rate, occurrence of hyperopia. But this is a temporary change, with the restoration of normoglycemia and disappear quickly, not a permanent change. The refractive mutation is often found in juvenile patients high blood glucose fluctuation.

Insulin Local reaction

The injection of local skin redness, fever and subcutaneous nodules, NPH or PZI in the initial treatment period within a few weeks, due to the presence of induced protein and other impurities, change parts may disappear, does not affect curative effect.
2 Subcutaneous fat atrophy Or hyperplasia, fat atrophy into depression, lack of sebum, more common in young women and children with thigh and abdominal wall subcutaneous injection site; increase the generation of lumps, more common in male hip injection site, sometimes a tingling, can affect the absorption, to replace the injection site and ensure treatment.

Insulin Drug resistance

Very few patients have insulin resistance, daily insulin requirement is more than 200U, which lasted 48 hours, and no ketoacidosis And other Endocrine disease The cause of secondary diabetes is called insulin resistance. This group does not include obesity, infection, liver disease, Hemochromatosis , Leukemia , Rheumatoid arthritis Fat atrophy caused by diabetes, such as drug resistance. immune reaction Because, after the injection of insulin in the blood Anti insulin antibody In general, which belongs to the IgG class, especially in the Bovine insulin Easy to produce. Thus, the insulin resistance and the pathophysiology of not insulin resistance Confused.
Treatment scheme:
The use of single component Human insulin Can significantly reduce the antibody production, ease Drug resistance ;
The oral anti to try Diabetes Combination of drugs and their;
The antibody concentration was significantly higher in the patients, when necessary to try Prednisone 30mg, ~ 40mg/d, points 3 times, mostly also can significantly reduce from 1 to 2 weeks after the effective dose of insulin, decreasing, stop prednisone. The course of treatment, need close observation and blood glucose, so as to avoid the occurrence of repeated serious resistance to fade in Hypoglycemia .
Insulin treatment nephropathy Can only be said to be hypoglycemic patients, when in use, must often detect blood sugar Once found, hypoglycemia, should timely adjust the dose of insulin.