Complementary Interactions between Insulin and Glucagon

In this article we will discuss about complementary interactions between insulin and glucagon.

Role of Insulin:

Insulin influences carbohydrate metabolism mainly in the liver and muscles. The binding of insulin with the receptor protein may re­duce intracellular cAMP in the target cells either by depressing the membrane bond adenylate cyclase or by stimulating the mem­brane associated phosphodiesterase that destroys cAMP.

The fall in cAMP may de­press specific protein kinases and thereby alter ribosomal translation of protein and activates enzymes like phosphorylase and glycogen synthetase.

Physiological actions of insulin exerts fol­lowing functions regarding carbohydrate metabolism:

1. Glycogenesis:

Insulin stimulates glyco­genesis from glucose, in both skeletal muscles and the liver.

This process is ini­tiated by:

(a) Activating protein phos­phatase which dephosphorylates and thereby activates glycogen synthetase,

(b) Inducing glycogen synthetase and glucokinase and

(c) By enhancing hexokinase II activity in muscles.

2. Glycogenolysis:

Insulin inhibits break­down of glycogen to glucose and de­presses the release of glucose from the liver into the blood.

This mechanism:

(a) Activates protein phosphatase-l which dephosphorylates and inacti­vates glycogen phosphorylase.

(b) Represses glucose-6-phosphatase, the final enzyme of the pathway.

3. Gluconeogenesis:

By inhibiting gluconeogen the conversion of amino acids into glucose in the liver hepatic glucose output is reduced. Insulin accomplishes this in two ways—by decreasing the amount of amino acids in the blood that are available to the vit. for gluconeogen­esis and by imbibing hepatic enzymes required for converting amino acids into glucose.

Inhibition of gluconeogenesis takes place because it:

(a) Activates protein phosphatase which, dephosphorylates and inactivates fructose 2, 6-bi-phosphatase leading to an increased intracellular concen­tration of fructose 2, 6-bi-phosphate that allosterically inhibits fructose 1, 6- bi-phosphatase of gluconeogenesis.

(b) Represses pyruvate carboxylase, PEP carboxykinase, fructose 1, 6- bi-phosphatase and glucose-6-phosphatase, all these enzymes lower the transcription rates of their respective genes.

4. Glycolysis:

Insulin enhances glyco­lysis in muscle, liver, adipocytes etc. because it:

(a) Induces phosphofructokinase-1 and pyruvate kinase of that pathway by enhancing the transcriptions of genes,

(b) Activates a phosphoprotein phos­phatase which dephosphorylates and thereby activates pyruvate kinase and

(c) Enhances muscle hexokinase II ac­tivity.

5. Glucose transport:

Insulin enhances the rate of glucose transport from extracel­lular fluid into muscles adipose tissue, mammary glands and other tissues across their plasma membrane. Glucose transport between the blood and cells is accomplished by means of plasma membrane carrier known as glu­cose transporters (GLUT).

GLUT can be classified into four types according varia­tion of amino acid sequences—GLUT I, II, III and IV. GLUT I transports glucose across the blood brain barrier, GLUT II transfers into the adjacent blood stream the glucose that has entered the kidney and intestinal cells by means of the co transport carriers, GLUT III is the main transporter of glucose into neurons and GLUT IV is the only type of glucose transporter that is responsive to insulin.

Factors Controlling Insulin Secretion:

Increased blood glucose concentration, blood amino acids concentration and gastro intestinal hormones are the major control­ling factors of insulin secretion. Somatosta­tin of pancreatic delta cells also controls the secretion of insulin.

Following schematic representation shows the control of insulin secretion (Fig. 10.12).

Role of Glucagon:

Glucagon is an anti-insulin hormone. The most important function is to increase the blood glucose concentration.

This hormone binds to glucagon receptors an the plasma membrane of hepatocytes and adipocytes. Glucagon activates the adenylate cyclase- cAMP system in the membrane to enhance the cytoplasmic concentration of cAMP which acts as the second messenger. cAMP then activates protein kinases which phosphorylate and modulate the activities of spe­cific cellular proteins.

Physiological function of glucagon on carbohydrate metabolism is given below:

1. Glycogenolysis in liver:

Hypoglycemic condition or in starvation, glucagon ac­tivates glycogen phosphorylase in the liver to reduce glycogen synthesis. Glu­cagon has no effect an glycogen phos­phorylase of muscle cells.

2. Gluconeogenesis in liver:

Glucagon in­creases hepatic gluconeogenesis from products of catabolism of proteins (amino acids) by inducing gluconeogenic en­zymes like pyruvate carboxylase, fruc­tose 1, 6-di-phosphatase (FD Pase).

3. Inhibition of glycogenesis:

Glucagon suppresses glycogen synthase which in-turn inhibits glycogenesis in liver.

Insulin and glucagon work as a team to maintain blood glucose:

Physiologists believe that the insulin secret­ing β-cells and the glucagon secreting α-cells as a coupled antagonistic endocrine system whose combined secretory output is a ma­jor factor in regulating glucose metabolism. Thus a direct negative feedback relationship between blood glucose concentration and the α-cells rate of secretion, but it is in the opposite direction of the effect of blood glu­cose on β-cells (Fig. 10.13).

Homeostatic condition of blood glucose level in the blood is maintained insulin and glucagon (Fig. 10.11). Insulin decreases blood sugar level, whereas glucagon in­creases blood sugar level.

Two physiologi­cal conditions are chiefly responsible:

1. During well fed stage:

Dietary carbo­hydrates stimulate insulin which in-turn stimulates synthesis of glycogen from glucose or glycogenesis. Thus blood glu­cose is lowered down by activating gly­cogen synthase.

2. During starvation:

This situation (hy­poglycemia) stimulates glucagon secre­tion and activating hepatic phosphory­lase for glycogenolysis. The product glu­cose is then quickly diffused in the blood to raise sugar level.