Insulin

• Increased transport of glucose, amino acids, and K+ into insulin-sensitive cells

• Stimulation of protein synthesis
• Inhibition of protein degradation
• Activation of glycolytic enzymes and glycogen synthase
• Inhibition of phosphorylase and gluconeogenic enzymes

• Increase in mRNAs for lipogenic and other enzymes

Inulin is a polysaccharide composed of fructose units. Inulin is filtered at the glomerulus of the kidney but is neither secreted nor reabsorbed by the tubule so it is used to measure the GFR.

• Ability to achieve a stable plasma concentration
• Freely filtered at the glomerulus
• Not reabsorbed, secreted, synthesized, or metabolized by the kidney.

A i.e. 1

B i.e. Hypokalemia

Effect of Insulin on K⁺ and PO43-

– Insulin increases the transport of potassium (K+) from plasma into cells by stimulating the Na⁺-K⁺ – ATPase pumps in cell membranes of muscle, liver and adipocytes. This results in lowering of plasma (extracellular) K+ concentration i.e. hypokalemiaQ.

– Infusions of insulin (and glucose) significantly lower the plasma K+ levels in normal individuals and are used for temporaty relief of hyperkalemia in patients with renal failure, waiting for dialysis.

– Hypokalemia often develops when patients with diabetic acidosis are treated with insulin.

– Insulin induces rapid entery of glucose into cells, a process which is followed by phosphorylation reaction in glycolytic pathway, lowering the intracellular concentration of inorganic phosphate, and therefore promotes phosphate (P0³–₄) entry into cells. This is how insulin 1/t hypophosphatemia (decrease plasma /ECF PO43-)

C i.e. Required for transport of glucose, aminoacid, K⁺ & Na+

A i.e. 3^rd month

A i.e. Decreased levels of cyclic AMP

C i.e. Inhibits Pyruvate dehydrogenase

A i.e. Glucose B i.e. Vagal Stimulation C i.e. Acetyl choline

Insulin

Embryology

Insulin containing granules can be identified in the human fetal pancreas by 9 to 10 weeks and detectable in fetal plasma by 12 weeksQ. Glucagon secretion begins by 8^tt week. Thyroxin secretion begins by 10^th to 12^th week.

Substance with Insulin like Activity

• Insulin
• Proinsulin
• Nonsuppressible insulin-like activity (NSILA)

– Low-molecular-weight fraction

IGF-I

IGF-II

– High molecular-weight fraction (mostly IGF bound to protein)

Insulin causes hypoglycemia. Hormones causing hyperglycemia (opposite action)

– CatecholaminesQ

(epinephrine, norepinephrine)

–  GlucagonQ

–  Growth hormoneQ, ACTH

–  Glucocorticoids

–  Thyroid hormonesQ

Principal Actions

Rapid (seconds)

–  Increased transport of glucose, amino acids, and K+ into insulin-sensitive cellsQ

Intermediate (minutes)

–  Stimulation of protein synthesis

–  Inhibition of protein degradation

– Activation of glycolytic enzymes and glycogen synthaseQ

– Inhibition of phosphorylase and gluconeogenic enzymesQ

Delayed (hours)

– Increased in mRNAs for lipogenic and other enzymes Insulin Stimulates lipogenesis by

– Increasing acetyl – Co A carboxylase activityQ, (most important enzyme in regulation of lipogenesis). This allosteric enzyme is activated by citrate, which increases in concentration in well fed state and is an indicator of a plentiful supply of acetyl CoA.

– Increasing transport of glucose into cellsQ like

adipose tissue.

– Increasing availability of pyruvate for fatty acid synthesis and glycerol 3 phosphate for easterificationQ of newly formed fatty acids.

– Activates pyruvate dehydrogenase in adipose tissue but not in liverQ.

– Decreases intracellular C- AMP levelQ – thus inhibitibiting lipolysis in adipose tissue and thereby reducing concentration of plasma free fatty acid and thus long chain acetyl CoAQ, an

inhibitor of lipogenesis.

Effects on Various Tissue

A i.e. Gluconeogenesis

D i.e. Ketogenesis

A  i.e. Active lipoprotein lipase

B i.e. Pyruvate carboxylase

Insulin increases lipogenesis (i.e. FA, TG & glycerol P synthesis) and decrease lipolysis and so free fatty acid levelQ

–  Insulin activate acetyl CoA carboxylase (rate limiting enzyme of FA synthesis), activate lipoprotein lipase (so increasing TG synthesis) but inhibits hormone sensitive lipase.Q

– Insulin decreases gluconeogenesis by inactivating pyruvate carboxylaseQ etc and increases glycolysis by inducing phosphofructokinase and pyruvate kinase enzymesQ.

B i.e. Heart

B i.e. T permeability across cell membrane against glucose gradient

Insulin increases glucose uptake by increasing the number of glucose transporter in cell membrane. Direct insulin stimulated glucose uptake is mediated by Glut 4 and is seen only in:

1. Muscle: Skeletal muscleQ and cardiac muscleQ
2. Adipose tissueQ

Glucose Transporters In Mammals

Insulin does not cross placenta

Ans is ‘c’ i.e. insulin binds to a receptor molecule on the outer surface of the plasma membrane which activates the tyrosine kinase that is the cytosolic domain of the receptor.

o Insulin receptors are membrane receptor of tyrosine kinase enzyme linked type. Their hormone binding site is extracellular and effective domain (i.e. tyrosine kinase) is intracellular.

o Insulin binds at extracellular site (outer surface of plasma membrane) and this binding activates intracellular (cytoso­lic) domain, i.e., tyrosine kinase

Ans. is ‘c’ i.e., Neutral

o Initially there were neutral and acidic preparations of insulin. Now only neutral insulin preprations are available, also known as regular insulin, except glargine (supplied at acidic pH-4)

Ans. is ‘d’ i.e., Regular insulin

o All preparations are administered by S.C. route except regular insulin which can be given

Ans. is ‘c’ i.e., Actrapid

o Actrapid preparations are there for Highly purified mono-component insulin and Human insulin.

o Insulin analogues are Insulin lispro, insulin aspart, insulin glulisine and insulin glargine.

Ans. is ‘c’ i.e., Glargine

1. Rapid acting Insulin          —-> Insulin lispro, Insulin aspart, Insulin glulisine.
2. Short acting                     —-> Regular (soluble) insulin, semilente insulin.
3. Intermediate acting          —-> Insulin zinc suspension (Lente), Neutral protamine hagedorn (isophane insulin).
4. Long acting                      —-> Protamin zinc insulin, Insulin glargine, Insulin determir

Note : A mixture of soluble insulin and isophane insulin is called biphasic insulin.

Ans. is ‘a’ i.e., Insulin glargine

• Long acting insulin are : Protamine zinc insuling, Insulin glargine, Insulin determir.

Ans. is ‘c’ i.e., NPH insulin

Ans. is ‘d’ i.e., Glargine

o All insulin preparations are supplied at neutral pH (7.2-7.4) except glargine (supplied at pH 4.0); therefore, glargine cannot be mixed with any insulin.

Ans. is ‘b’ i.e., Albuminuria

Adverse effects of insulin

1)  Hypoglycemia

2)  Local reactions: Swelling erythema, stinging, injection site lipodystrophy.

3)  Allergy: Urticaria, angioedema and anaphylaxis.

4)  Edema

Ans. is ‘a’ i.e., Insulin

o Insulin and insulin like growth factor stimulate fetal growth.

o Thyroxine has no effect on linear growth but it has effect on skeletal maturation.

o Fetal or maternal GH is not essential for fetal growth in utero.

Ans. is ‘b’ i.e., Caudal Regression

`The fetal malformations seen in Caudal regression syndrome are the most typical seen in cases of maternal diabetes’.- Early detection of caudal regression syndrome, D. Subtil et al.

Caudal regression :

o Caudal regression syndrome (CRS) is a rare malformative syndrome seen mainly in cases of maternal diabetes with poor metabolic control.

o This syndrome associates vertebral agenesis of variable level with genito-urinary and digestive malformations. These abnormalities are related to the impaired development of the mid-posterior axis mesoderm

Ans. is ‘b’ i.e., 25-50%

o Several factors influence the initial daily insulin dose per kilogram of body weight.

o The dose is usually higher in pubertal children.

o It is higher in those who have to restore greater deficits of body glycogen, protein, and fat stores and who, therefore, have higher initial caloric capacity.

o On the other hand, most children with new-onset diabetes have some residual a-cell function (the “honeymoon” period), which reduces exogenous insulin needs.

o Residual f3-cell function usually fades within a few months and is reflected as a steady increase in insulin requirements and wider glucose excursions.

o The initial insulin schedule should be directed toward the optimal degree of glucose control in an attempt to duplicate the activity of the (3-cell.

o Acceptable glucose control can be obtained with new insulin analogs used in a basal-bolus regimen, that is, with slow‑ onset, long-duration background insulin for between-meal glucose control and rapid-onset insulin at each meal.

Bolus insulin

Age (yr)             Target glucose Total daily              Basal insulin,          Units added                Units added

MOO                         insulin                  % of total                  per 100 mg/dl          per 15 g at

(U/kg/d)                daily dose                  above target            meal

 o Newly diagnosed children in the “honeymoon” may only need 60-70% of a full replacement dose. Total daily dose per kg increases with puberty.

Answer is B (Infusion of insulin and glucose):

‘Intravenous insulin is the fastest way to lower serum potassium levels’

Answer is D (Regular Insulin):

The drug of choice for managing hyperglycemia in diabetic ketoacidosis is regular insulin

The drug of choice for managing hyperglycemia in diabetic ketoacidosis is regular insulin because of its rapid but short- duration actions. Regular (fast-acting) insulin is the primary insulin preparation used in the management of Diabetic Ketoacidosis (DKA) and is the only insulin that should be given intravenously or intramuscularly.

Lente insulin is a longer-acting form of insulin than regular and should not be used. Oral Hypoglycaemic agents are never used for initial management of Diabetic Ketoacidosis.

Answer is A (Regular insulin):

The drug of choice for managing hyperglycemia in diabetic ketoacidosis is regular insulin

The drug of choice for managing hyperglycemia in diabetic ketoacidosis is regular insulin because of its rapid but short- duration actions. Regular (fast-acting) insulin is the primary insulin preparation used in the management of Diabetic Ketoacidosis (DKA) and is the only insulin that should be given intravenously or intramuscularly. Lente insulin is a longer-acting form of insulin than regular and should not be used. Oral Hypoglycaemic agents are never used_, for initial management of Diabetic Ketoacidosis.

Answer is C (Insulin) :

‘Diabetic ketoacidosis cannot be reverted without insulin’ – Harrison

The patient in the above question is a definite case of diabetic Ketoacidosis, as suggested by increased blood sugar (Diabetes) and presence of sugar & ketones in urine (ketoacidosis) in an obese (type I) diabetic.

Diabetic ketoacidosis cannot be reverted without insulin

Remember:

Apart from diabetes the only other common ketoacidotic state is alcoholic ketoacidosis. Alcoholic ketoacidosis is invariably associated with hypoglycemia.

A plasma glucose estimation usually is required to delineate such patients. Most patients have a plasma glucose, levels of less than 150 mg/dl. Hyperglycemia may occur but is usually mild, & rarely if ever exceeds 300 mg/dl. It is important to know this distinction as, in contrast to diabetic acidosis this syndrome is rapidly reversed by the intravenous administration of glucose.

Answer is A (Insulin):

Presence of sugar and ketones in urine and the presence of hyperglycemia (400 mg Glucose) suggests a diagnosis of Diabetic ketoacidosis. The treatment of choice in Diabetic ketoacidosis is Insulin.

Answer is A (Hypokalemia):

Insulin causes IC to enter cells with a resultant lowering of extracellidar IC concentration (Hypokalemia)

Relation of Insulin to Potassium

• Insulin causes K to enter cells with a resultant lowering of the extracellular K⁺ concentration (Hypokalemia)
• Infusion of insulin and glucose significantly lower the plasma K⁺ level in normal individual (Hypokalemia)
• Infusion of insulin and glucose is very effective for the temporary relief of hyperkalemia
• The reason for intracellular migration of K⁺ is still uncertain. However it is belived to result from increase in the activity of Na+ – K⁺ ATPase in cell membranes so that more K⁺ is pumped into cells

Answer is A (Increased Glucagon secretion):

Insulin Inhibits glucogon release by pancreatic alpha cells.

Insulin facilitates increased cellular uptake glucose into most tissues (insulin sensitive tissues) with a resultant lowering of serum glucose (Hypoglycemia). Insulin enhance fatty acid synthesis and inhibits lipolysis.

Answer is C (CDNA of pancreatic cell)

Answer is A (Hypokalemia):

Insulin causes IC to enter cells with a resultant lowering of extracellular IC⁺ concentration (Hypokalemia)

Relation of Insulin to Potassium (Ganong 22^nd/338)

• Insulin causes IC to enter cells with a resultant lowering of the extracellular K⁺ concentration (Hypokalemia)
• Infusion of insulin and glucose significantly lower the plasma IC level in normal individual (Hypokalemia)
• Infusion of insulin and glucose is very effective for the temporary relief of hyperkalemia
• The reason for intracellular migration of IC is still uncertain. However increase the activity of Na⁺ – K⁺ ATPase in cell membranes so that more IC is pumped into cells.

Ans. A: RBC

Insulin facilitates entry of glucose into muscle, adipose, and several other tissues.

The only mechanism by which cells can take up glucose is by facilitated diffusion through a family of hexose transporters. In many tissues – muscle being a prime example – the major transporter used for uptake of glucose (called GLUT4) is made available in the plasma membrane through the action of insulin.

The net effect of insulin on lipid metabolism is to reduce the release of fatty acids from the stored fat.

Among the tissues, adipose tissue is the most sensitive to the action of the insulin

Lipogenesis

• It is the process by which acetyl-CoA is converted to fats.
• The former is an intermediate stage in metabolism of simple sugars, such as glucose.
• Through lipogenesis, the energy can be efficiently stored in the form of fats.
• Lipogenesis encompasses the processes of fatty acid synthesis and subsequent triglyceride synthesis (when fatty acids are esterified with glycerol to form fats).
• The products are secreted from the liver in the form of very-low-density lipoproteins (VLDL)
• Fatty acids synthesis starts with acetyl-CoA and builds up by the addition of two carbon units.
• The synthesis occurs in the cytoplasm in contrast to the degradation (oxidation), which occurs in the mitochondria.
• Man^y of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthetase.

Control and regulation

• Insulin is an indicator of the blood sugar level of the body, as its concentration increases proportionally with blood sugar levels.
• Thus, a large insulin level is associated with the fed state.
• As one might expect, therefore, it increases the rate of storage pathways, such as lipogenesis.
• Insulin stimulates lipogenesis in two main ways:
• The enzymes pyruvate dehydrogenase (PDH), which forms acetyl-CoA, and acetyl-CoA carboxylase (ACC), which forms malonyl-CoA, are obvious control points.
• These are activated by insulin.
• So a high insulin level leads to an overall increase in the levels of malonyl-CoA, which is the substrate required for fatty acids synthesis.
• PDH dephosphorylation

In association with insulin, chromium promotes the utilization of glucose

Chromium is a component of a protein namely chromodulin which facilitates the binding of insulin to cell receptor sites

Chromium

• It is an essential nutrient for the maintenance of normal glucose tolerance
• Its deficiency causes insulin resistance.
• Chromium administration has also been shown in several studies to lower glucose and insulin levels in patients with type 2 diabetes.
• It has been classified as not essential for mammals. (Cr (III) or Cr3+).
• Chromium deficiency is controversial or is at least extremely rare.
• It has been attributed to only three people on parenteral nutrition, which is when a patient is fed a liquid diet through intravenous drips.
• In contrast, hexavalent chromium (Cr (VI) or Cr6+) is very toxic and mutagenic when inhaled.
• Cr (VI) has not been established as a carcinogen when in solution, although it may cause allergic contact dermatitis (ACD).

Dietary supplements for chromium include chromium (III) picolinate, chromium (III) polynicotinate, and related materials.

• Glutathione peroxidase requires selenium
• Copper is an important constituent of catalse, cytochrome oxidase and tyrosinase.
• Zinc is also necessary for the storage and secretion of insulin

Ans. B i.e. 10 minutes

Degradation of insulin

• Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment, or it may be degraded by the cell.
• The two primary sites for insulin clearance are the liver and the kidney.
• The liver clears most insulin during first-pass transit, whereas the kidney clears most of the insulin in systemic circulation.
• Degradation normally involves endocytosis of the insulin-receptor complex, followed by the action of insulin-degrading enzyme.
• An insulin molecule produced endogenously by the pancreatic beta cells is estimated to be degraded within about one hour after its initial release into circulation (insulin half-life – 4-6 minutes)

Ans. D: Insulin Lispro

Insulin is divided into four basic types based on how quickly it works and how long it lasts.

• Rapid-acting insulin (such as lispro/aspart/glulisine) is the fastest and shortest acting. It is taken as several daily injections up to 5 minutes before meals or just after eating. Rapid-acting insulin reaches its maximum effect in 1-2 hour and works for 2 to 5 hour.
• Short-acting insulin (such as regular insulin), which is taken 30 to 60 minutes before a meal, reaches its maximum effect in 2 to 4 hours and works for 6 to 8 hours.
• Intermediate-acting insulin (such as lente or Neutral Protamine Hagedorn) starts to work in 1 to 2 hours, reaches its maximum effect in 8 to 10 hours, and works for 20 to 24 hours. It may be used in the morning to control blood sugar levels for the first part of the day or in the evening to control blood sugar levels during the night.
• Long-acting insulin (such as ultra-lente or glargine) begins to work very slowly but lasts for 24 to 36 hours. Long-acting insulin usually has its maximum effect at 14 to 20 hours.

Insulin suppresses glucose-6-phosphatase gene.

Glucose-6-phosphatase activity is increased in low insulin/glucagon level.

Glucocorticoids, glucagon, epinephrine are inducers of glucose-6-phosphatase whereas insulin is repressor.

Insulin upregulates the transcription of glucokinase, phosphofructokinase, and pyruvate kinase, while glucagon downregulates their transcription.

Glucose-6-phosphatase plays an important role in the regulation of hepatic glucose production, and insulin suppresses glucose-6-phosphatase gene.

Ans. is ‘a’ i.e., GLP-1

• Recently, attention has been focused on glucagon – like polypeptide 1 (7-36) (GLP-1 [7-36]) as an additional gut factor for insulin secretion and GLP-1 (7-36) is more potent insulinotropic hormone.

Regulation of insulin secretion

Factors affecting insulin secretion are : –

i) Simulating insulin secretion :- Glucose; Mannose; Amino acids (arginine, leucine); Intestinal hormones (GIP. Gastrin, Secretin, CCK, GLP -1); β-keto acids; Parasympethetic stimulation (acetylcholine); cAMP; β-adrenergic stimulation; theophylline; Sulfonylureas; and certain endocrine hormones like growth hormone, Glucagon and glucocorticoids.

ii) Inhibiting insulin secretion : – Somatostatin; 2-deoxyglucose; mannoheptulose; a-adrenergic stimulation, P-adrenergic inhibitors; galanin; Diazoxide; Thiazide diuretics; K⁺ depletion; Phenytoin; Alloxan; microtubule inhibitors; and insulin itself.

Ans. is ‘a’ i.e., Adipose tissue

• Insulin stimulates the uptake of glucose by myocytes (skeletal muscle, cardiac muscles), adipocytes (adipose tissue) and hepatocytes. Tissues that do not depend on insulin for glucose uptake include brain, erythrocytes (RBC), the epithelial cells of kidney & intestine, Liver, and Cornea & lens of eye.
• The mechanism through which insulin increases glucose uptake is different in different tissues. In the muscle and adipose tissues, insulin increase facilitated diffusion by increasing glucose transporter (GLUT4) on the cell membrane.
• In the liver, insulin stimulates glucose entry into hepatocytes indirectly by induction of glucokinase so that the glucose entering the liver cells is promptly converted to glucose – 6 – phosphate (glucose trapping). This keeps the intracellular glucose concentration low and favours entry of glucose into the liver. Thus, though the liver do not depend on insulin for glucose uptake, insulin stimulates glucose entry into hepatocytes. That means glucose entery can occur in liver without the action of insulin, but this is facilitated by insulin. On the other hand, myocytes (skeletal and cardiac muslces) and adipocytes (adipose tissue) are dependent on insulin for glucose uptake.

Ans. is ‘c’ i.e., Increased insulin secretion from beta-cells of pancreas

Insulin dependent glucose uptake is through GLUT-4 and is seen in :‑

1) Skeletal muscles

2) Cardiac muscles (heart)

3) Adipose tissue

Ans. is ‘a’ i.e., It produces a smooth peakless effect

InsuinGlargine

• It is long acting biosynthetic insulin.
• It remains soluble at pH 4 of the formulation and precipitates at neutral pH on subcutaneous administration.
• Onset of action is delayed.
• It produces a smooth peakless effect.
• It is suitable for once daily administration.
• Low incidence of night time hypoglycemia.
• It does not control meal time yperglycemia.

Ans. is ‘d’ i.e., Somatostatin

Ans. is ‘c’ i.e., Induction of lipogenesis

ACTIONS OF INSULIN

• Insulin affects the metabolism of carbohydrates, lipids and proteins.

Effects on carbohydrate metabolism

The overall effect of insulin is to decrease blood glucose level. Insulin increases the utilization of glucose and decreases its production by its following actions : –

i) Stimulation of oxidation of glucose by glycolysis especially in the liver and skeletal muscle.

ii) Stimulation of glycogenesis i.e., insulin favours conversion of glucose into its storage form, glycogen. This action is seen in both liver and muscles.

iii) Inhibition of gluconeogenesis.

• Insulin stimulates the uptake of glucose by myocytes (skeletal muscle, cardiac muscles), adipocytes (adipose tissue) and hepatocytes. Tissues that do not depend on insulin for glucose uptake include brain, erythrocytes (RBC), the epithelial cells of kidney & intestine, Liver, and Cornea & lens of eye.
• The mechanism through which insulin increases glucose uptake is different in different tissues. In the muscle and adipose tissues, insulin increase facilitated diffusion by increasing glucose transporter (GLUT4 ) on the cell membrane.
• In the liver, insulin stimulates glucose entry into hepatocytes indirectly by induction of glucokinase so that the glucose entering the liver cells is promptly converted to glucose – 6 – phosphate (glucose trapping). This keeps the intracellular glucose concentration low and favours entry of glucose into the liver. Thus, though the liver do not depend on insulin for glucose uptake, insulin stimulates glucose entry into hepatocytes. That means glucose entery can occur in liver without the action of insulin, but this is facilitated by insulin. On the other hand, myocytes (skeletal and cardiac muslces) and adipocytes (adipose tissue) are dependent on insulin for glucose uptake.

Increased uptake of glucose in the glucose has following effects :-

i) T Glycolysis :- It is due to induction of key enzymes of glycolysis by insulin. These key enzymes are glucokinase, phosphofructokinase and pyruvate kinase.

ii) Increased glycogen synthesis (glycogenesis) :- It is due to induction of glycogen synthase.

iii) Decreased glycogen break-down (Glycogenolysis) : – It is due to inhibition of enzyme phosphorylase.

iv) Decreased gluconeogenesis :- It is due to inhibition of enzymes Pyruvate carboxylase, PEP carboxykinase, fructose 1, 6-bisphosphatase, glucose – 6 – phosphates.

Effects on lipid metabolism

• Insulin induces lipogenesis by inducing enzyme acetyl CoA carboxylase, the rate limiting enzyme in fatty acid synthesis. Triglyceride synthesis is increased by induction of lipoprotein lipase.
• Lipolysis (13-oxidation) is decreased due to inhibition of hormone sensitive lipase, so that the fat in the adipose tissue is not broken down. Thus free fatty acid and glycerol are decreased. Because of antilipolytic action insulin decreases ketogenesis.

There are two important lipases : –

i)  Lipoprotein lipase : – It hydrolysis the triglycerides of chylomicrons and VLDL into free fatty acid and glycerol in the vessels of skeletal muscles, cardiac muscles and adipose tissue. There FFA is taken up by the cells of these tissue and is converted back into the triglyceride and the FFA is stored as triglyceride. So, lipoprotein lipase is involved in the synthesis of triglyceride. Lipoprotein lipase is stimulated by insulin, therefore insulin stimulates triglyceride synthesis.

ii) Hormone sensitive lipase : – It is involved in lipolysis and cause degradation of stored triglyceride of adipose tissue into FFA and glycerol. FFA comes out into the blood raising the FFA levels of blood. Insulin inhibits hormone sensitive lipase therefore decreases FFA levels of blood.

Effects on protein metabolism

• Insulin stimulates synthesis of protein (anabolism) and inhibits protein breakdown (catabolism). Insulin increases the active transport of many amino acids into the tissue. In addition insulin increases protein synthesis by increasing the rate of synthesis of mRNA.

Ans. is `b’ i.e., Zn⁺⁺

Zinc ions are essential for the formation of hexameric insulin and hormone crystallization.

Following the synthesis of proinsulin, zinc promotes the formation of proinsulin hexamers and increases its solubility before conversion to insulin.

Proinsulin binds 30 zinc ions, of which 2 to 4 are coordinated within the molecule. These zinc ions appear to be important for the solubility of proinsulin hexamers.

With the removal of C-peptide from each proinsulin monomers, the resulting insulin increases its coordination of zinc to up to six ions per hexamer, which decreases its solubility and increases its crystallization within the secretory vesicle.

The insulin, stored as crystalline hexamer, is resistant from proteolytic attack within the vesicle.

Upon release of insulin into the bloodsteam, zinc is also released and the insulin becomes soluble in the blood.

Ans. is ‘c’ i.e., Intermidiate acting

Ans. is ‘c’ i.e., Heart 

Ans. is ‘b’ i.e., Insulin independent 

Ans. is ‘d’ i.e., Regular insulin