Abdul Khaliq Naveed, Farooq Ahmad Khan.
GLP-1 regulation of Glucagon, Somatostatin and Insulin in NIDDM patients: evidence of direct inhibition of a - cells by GLP-1.
Pak J Pathol Jan ;17(4):130-6.

Introduction: Glucagon-like peptide-1 (7-36) amide (GLP-1) is released from the gut into the circulation after meals and is the most potent physiological insulinotropic hormone in man. In contrast to presently available therapeutic agents for non-insulindependent diabetes mellitus (NIDDM), GLP-1 has the advantages of both suppressing glucagon secretion and delaying gastric emptying. Materials and methods: We report first study of subcutaneous GLP-1 treatment to determine the opitmum dose required to control the NIDDM. Seven patients, with poorly controlled NIDDM were entered in the study who visited at four visits with intervals of 2-4 days and received saline 40, 100 and 200 nmol subcutaneous GLP-1, immediately after meals A standerdized test meal was given. Results: A significant hypoglycaemic response (p<0.05) was achieved in patients given 40, 100 and 200 nmol GLP-1. An increase in insulin levels (p<0 05) was observed as compared to control, when 100 and 200 nmol GLP-1 was given. There was no significant difference between insulin and glucose responses when 100 and 200 nmol of GLP-1 were compared with each The glucagon levels were significant less (p< 0.05) in patients, given 100 and 200 nmol doses as compared to control. Glucagon inhibitory response to GLP-1, when given in doses of 200 nmol was more (p< 0.05) than 100 nmol GLP-1. Somatostatin levels decreased dose dependently by GLP-1 infusions. Conclusion: It is concluded that suppression of glucagon secretion and inhibition of somatostatin corresponded to dose of GLP-1 used. There was no significant difference in glucose and insulin levels between 100 and 200 nmol GLP-1 doses. Therefore, present study has helped in ascertaining the optimum dose for GLP-1 i.e. 100 nmol. Down regulation of GLP-1 receptors on a cells occurred at higher dose while, A and D cells inhibition occurred dose dependently. These results revealed that GLP-1 affects A and D cells directly and also through stimulation of a cells. These findings will significantly contribute in the possible role of GLP-1 as a therapeutic agent in diabetic patient.

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