Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans.

Abstract

INTRODUCTION:

Impaired secretion of glucagon-like peptide 1 (GLP-1) has been suggested to contribute to the deficient incretin effect in patients with type 2 diabetes. It is unclear whether this is a primary defect or a consequence of the hyperglycemia in type 2 diabetes. We examined whether acute hyperglycemia reduces the postprandial excursions of gastric inhibitory polypeptide (GIP) and GLP-1, and if so, whether this can be attributed to changes in gastric emptying.

PATIENTS AND METHODS:

Fifteen nondiabetic individuals participated in a euglycemic clamp and a hyperglycemic clamp experiment, carried out over 285 min. A mixed meal was ingested after 45 min. Plasma concentrations of glucose, insulin, C-peptide, glucagon, triglycerides, GIP, and GLP-1 were determined, and gastric emptying was assessed using a (13)C-octanoate breath test.

RESULTS:

Glucose levels were 160 +/- 1 mg/dl during the hyperglycemic clamp experiments and 83 +/- 3 mg/dl during the euglycemia (P < 0.0001). Glucose infusion rates were higher during hyperglycemia, but meal ingestion led to a decline in glucose requirements in both experiments (P < 0.0001). Insulin and C-peptide levels were higher during the hyperglycemic clamp experiments (P < 0.0001), whereas glucagon levels were higher during euglycemia (P < 0.0001). The postprandial increases in GIP and GLP-1 concentrations were 46 and 52% lower during the experiments with hyperglycemia (P = 0.0017 and P = 0.021). Hyperglycemia also elicited a significant delay in gastric emptying (P < 0.0001).

CONCLUSIONS:

Hyperglycemia acutely reduces the postprandial levels of GIP and GLP-1, possibly through a deceleration of gastric emptying. This supports the concept that reduced incretin levels in some patients with type 2 diabetes are a consequence rather than a cause of type 2 diabetes.

• Authors: Kirsten Vollmer, Husai Gardiwal, Bjoern A Menge, Oliver Goetze, Carolyn F Deacon, Wolfgang E Schmidt, Jens J Holst, Juris J Meier
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 94 Issue 4 Pg. 1379-85 (Apr 2009) ISSN: 1945-7197 [Electronic] United States
• PMID: 19174495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• C-Peptide
• Cholesterol, HDL
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• Glucagon

Topics

• Adult
• Body Mass Index
• C-Peptide (blood)
• Cholesterol, HDL (blood)
• Female
• Gastric Emptying
• Gastric Inhibitory Polypeptide (blood)
• Glucagon (blood)
• Glucagon-Like Peptide 1 (blood)
• Glucose Clamp Technique
• Humans
• Hyperglycemia (blood, physiopathology)
• Kidney Function Tests
• Liver Function Tests
• Male
• Postprandial Period
• Reference Values
• Young Adult