Blood Glucose Regulation

Dr.S.SethupathyProfessor of Biochemistry,

RMMC ,AU

Blood Glucose Regulation Hypoglycemia kills the patient immediately whereas hyperglycemia kills slowly by producing complications and organ failureSo it is essential to maintain blood glucose at optimum level

Fasting plasma glucose is 70-100 mg/dl (after 12-14 hrs fasting). When plasma glucose estimated by enzymatic method drops below 40 mg/dl results in hypoglycemia

When fasting plasma glucose level is 101-125 mg/dl, it is called impaired fasting glucose and when more than 126 mg/dl it is labeled as diabetes mellitus

After a meal, blood glucose raises and it is normally less than 140 mg/dl at 2 hrs (post prandial).If it is between 141 and 200 mg/dl, it is called as impaired glucose tolerance. If it is more than 200 mg/dl, it is labeled as diabetic .

How blood glucose is brought down to normal level in fed state?1. By transport of glucose into the cellsGlut-2 transporter in liver is freely permeable to glucose.Insulin increases the transport of glucose across cell membranes of adipose tissue and muscle by stimulating glut-4-transporter

2. Stimulation of glycolysisIn liver, insulin increases the glycolysis by inducing the synthesis of the following enzymesGlucokinasePhosphofructokinase-1Pyruvate kinase

Stimulation of glycogenesisIn liver and muscle, insulin stimulates glycogenesis by activating glycogen synthase through dephosphorylation of the enzyme.Stimulation of lipogenesisInsulin stimulates the acetyl-CoA-carboxylase, the rate limiting enzyme in fatty acid synthesis mainly in liver, and to a lesser extent in adipose tissue.Stimulation of protein synthesisInsulin increases protein synthesis.

How blood glucose level is maintained normally in fasting state ?Reduction of Uptake of glucose by less vital tissuesDue to low insulin level, glucose uptake by muscle and adipose tissue is reduced due to inhibition of glut-4-transporter Stimulation of glycogenolysisGlucagon through its receptors in liver cells activates phosphorylase enzyme through cyclic AMP.

Epinephrine also activates phosphorylase in liver and muscle through cAMPBoth glucagon and epinephrine inhibit glycogenesis by phosphorylating the enzyme glycogen synthase.Thyroxin also increases hepatic glycogenolysis.

Stimulation of gluconeogenesisGlucagon stimulates gluconeogenesis from amino acids through alanine-glucose cycleLactate forms glucose in liver through Cori cycle - Lactate-glucose cycleEpinephrine promotes glycogenolysis in muscle and on catabolism, lactate produced is carried to liver for gluconeogenesis

Glucocorticoids increase protein catabolism to provide glucogenic amino acids for gluconeogenesis and it also increases the hepatic uptake of amino acidsGlucocorticoids also inhibit the utilization of glucose by extra hepatic tissues.Growth hormone decreases glucose uptake by muscle and ACTH decreases glucose utilization by the peripheral tissues

Renal control mechanismThe capacity of renal tubular system to reabsorb glucose is limited to a rate of about 350 mg/min known as tubular maximum for glucose (TMG)

If the blood glucose level goes beyond 160 - 180 mg/dl complete renal tubular reabsorption does not occur and so glucose appears in urine. This range of blood glucose level is known as renal threshold value for glucose

GlycosuriaExcretion of detectable amount of sugar in urine. It includes glucosuria, fructosuria, galactosuria, lactosuria, pentosuriaGlucosuriaExcretion of detectable amount of glucose in urine.Alimentary glucosuriaA rapid and transitory rise in blood glucose due to rapid absorption of glucose in the intestine after a meal result in glucosuria. It is harmless.e.g. In patients with partial gastrectomy

Renal glucosuriaThis is due to lowered renal threshold for glucose resulting in impaired tubular reabsorption of glucose. It is harmless. Blood glucose level will be normal in these patients.

Diabetic glucosuriaThis is due to hyperglycemia

Summary

Insulin decreases blood glucose level by 1. Increasing glycolysis2. Increasing glycogenesis3. Increasing lipolysis4. Increase glucose uptake by muscle and adipose tissue via GLUT-4

Glucagon and epinephrine

• These hormones increase blood glucose level by

• Increasing glycogenolysis• Increasing gluconeogenesis• Increase lipolysis

Oral Glucose Tolerance Test

It is the test to assess the ability an individual to metabolize a particular local of glucose which reflected by changes in the blood glucose level. It is useful to diagnose early cases of diabetes mellitus and for known cases of diabetes mellitus, it is not required .

Procedure• On high carbohydrate for 3 days prior to the

test• Fasting blood sample (10-12 hours of fasting)

is drawn• 75 gms glucose in 300 ml water to be taken

orally in 5-10 mins• Blood and urine samples are collected every ½

hr for 2 hours• Blood glucose is estimated• Urine is tested for glucose

Normal Diabetes

• OGTT CURVE• •

250-•• 200-• 180 -•

150-•• 100-• • 50-• • 0 • -ve ½ 1 11/2 2 Time (Hrs)• urine Sugar -ve -ve -ve -ve •

Diabetes• OGTT CURVE• •

250-•• 200-• 180 -•

150-•• 100-• • 50-• • 0 • -ve ½ 1 11/2 2 Time (Hrs)• urine Sugar -ve +ve +ve +ve •

Renal Glucosuria • OGTT CURVE• •

250-•• 200-• 180 -•

150-•• 100-• • 50-• • 0 • -ve ½ 1 11/2 2 Time (Hrs)• urine Sugar -ve +ve -ve -ve •

Thank you