Blood glucose regulation

Blood glucose regulation and OGTT for medical students

1. Blood Glucose Regulation Dr.S.Sethupathy Professor of Biochemistry, RMMC ,AU

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

3. 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

4. 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

5. 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 .

6. How blood glucose is brought down to normal level in fed state? 1 . By transport of glucose into the cells Glut-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

7. 2. Stimulation of glycolysis In liver, insulin increases the glycolysis by inducing the synthesis of the following enzymes Glucokinase Phosphofructokinase-1 Pyruvate kinase

8. Stimulation of glycogenesis In liver and muscle, insulin stimulates glycogenesis by activating glycogen synthase through dephosphorylation of the enzyme. Stimulation of lipogenesis Insulin 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 synthesis Insulin increases protein synthesis.

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

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

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

12. Glucocorticoids increase protein catabolism to provide glucogenic amino acids for gluconeogenesis and it also increases the hepatic uptake of amino acids Glucocorticoids 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

13. Renal control mechanism The 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

14. Glycosuria Excretion of detectable amount of sugar in urine. It includes glucosuria , fructosuria , galactosuria , lactosuria , pentosuria Glucosuria Excretion of detectable amount of glucose in urine. Alimentary glucosuria A 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

15. Renal glucosuria This 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 glucosuria This is due to hyperglycemia

16. Summary Insulin decreases blood glucose level by 1. Increasing glycolysis 2. Increasing glycogenesis 3. Increasing lipolysis 4. Increase glucose uptake by muscle and adipose tissue via GLUT-4

17. Glucagon and epinephrine These hormones increase blood glucose level by Increasing glycogenolysis Increasing gluconeogenesis Increase lipolysis

18. 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 .

19. 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

20. Normal Diabetes OGTT CURVE   250- 200-   180 - 150- 100-   50-   - ve ½ 1 11/2 2 Time (Hrs) urine Sugar - ve - ve - ve - ve  

21. Diabetes OGTT CURVE   250- 200-   180 - 150- 100-   50-   - ve ½ 1 11/2 2 Time (Hrs) urine Sugar - ve + ve + ve + ve  

22. Renal Glucosuria OGTT CURVE   250- 200-   180 - 150- 100-   50-   - ve ½ 1 11/2 2 Time (Hrs) urine Sugar - ve + ve - ve - ve  

23. Thank you