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


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.
Ludvik
B
B
Department of Medicine 3, University of Vienna Medical School, Austria. bernhard.ludvik@akh-wien.ac.at
Thomaseth
K
K
Nolan
J J
JJ
Clodi
M
M
Prager
R
R
Pacini
G
G
D000328:Adult; D000682:Amyloid / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D000682:Amyloid; D001786:Blood Glucose; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; D005947:Glucose