Inverse relation between amylin and glucagon secretion in healthy and diabetic human subjects

Eur J Clin Invest. 2003 Apr;33(4):316-22. doi: 10.1046/j.1365-2362.2003.01142.x.


Background: The role of amylin, which is cosecreted together with insulin by the pancreatic B-cells, in the pathogenesis of type-2 diabetes is still unclear. To elucidate a possible relation between amylin and glucagon we directly evaluated the respective prehepatic secretions following administration of a 75-g oral glucose load (OGL) in humans.

Materials and methods: We studied six healthy controls (C), six obese, insulin resistant subjects (O) and six patients with type 2 diabetes (D). Catheters were placed in the femoral artery and hepatic vein according to the hepatic vein catheterization technique. Splanchnic blood flow was assessed by infusion of indocyanine-green dye. The measured variables were analyzed by a general circulatory model for calculation of prehepatic secretion.

Results: The total amount of released glucagon was not different between the respective groups (20.5 +/- 2.3 in C, 27.7 +/- 5.1 in O and 27.9 +/- 5.4 micro g/4 h in D). When considered as the difference from the fasting profile, however, glucagon secretion was reduced by 3.5 +/- 14% in C, 25 +/- 12% in O and increased by 36 +/- 21% in D (P = 0.051, D vs. C). Amylin secretion was increased in O (1.10 +/- 0.15) vs. C (0.63 +/- 0.05, P < 0.05) and D (0.24 +/- 0.10 nmol, P < 0.01). Following glucose administration, glucagon secretion significantly inversely correlated with secretion of amylin (r = -0.6, P < 0.01), but not with that of insulin (r =-0.23, P = 0.36).

Conclusions: The inverse correlation between amylin and glucagon secretion suggests that amylin modulates glucagon secretion following oral glucose administration. This study proves for the first time a role of endogenous amylin in the regulation of glucose homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyloid / metabolism*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Glucagon / metabolism*
  • Glucose / administration & dosage
  • Glucose Clamp Technique / methods
  • Humans
  • Islet Amyloid Polypeptide
  • Islets of Langerhans / metabolism
  • Male
  • Middle Aged


  • Amyloid
  • Blood Glucose
  • Islet Amyloid Polypeptide
  • Glucagon
  • Glucose