Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients

J Diabetes Complications. 2015 Apr;29(3):413-21. doi: 10.1016/j.jdiacomp.2014.12.010. Epub 2014 Dec 26.


Aims: Hypersecretion of glucagon and reduced insulin secretion both contribute to hyperglycemia in type 2 diabetes (T2DM). However, the relative contributions of impaired glucagon and insulin secretions in glucose excursions at the various stages of T2DM development remain to be determined.

Methods: The responses of glucagon and insulin as well as those of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were examined before and after ingestion of glucose or mixed meal in Japanese subjects with normal or impaired glucose tolerance (NGT and IGT) and in non-obese, untreated T2DM of short duration.

Results: In OGTT, T2DM showed a rise in glucagon at 0-30 min, unlike NGT and IGT, along with reduced insulin. In MTT, all three groups showed a rise in glucagon at 0-30 min, with that in T2DM being highest, while T2DM showed a significant reduction in insulin. Linear regression analyses revealed that glucose area under the curve (AUC)0-120 min was associated with glucagon-AUC0-30 min and insulin-AUC0-30 min in both OGTT and MTT. Total and biologically intact GIP and GLP-1 levels were similar among the three groups.

Conclusions: Disordered early phase insulin and glucagon secretions but not incretin secretion are involved in hyperglycemia after ingestion of nutrients in T2DM of even a short duration.

Keywords: GIP; GLP-1; Glucagon; Hyperglycemia; Insulin.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Eating
  • Female
  • Food
  • Glucagon / metabolism*
  • Glucose Tolerance Test
  • Humans
  • Hyperglycemia / etiology*
  • Hyperglycemia / metabolism
  • Incretins / metabolism*
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Middle Aged
  • Postprandial Period*
  • Time Factors
  • Young Adult


  • Blood Glucose
  • Incretins
  • Insulin
  • Glucagon