Early-phase insulin secretion is disturbed in obese subjects with glucose intolerance.
The loss of early-phase insulin secretion is a characteristic feature of type 2 diabetes mellitus. The aim of this study is to examine when impairment of early-phase insulin secretion occurs and whether it can be related to increase in insulin resistance caused by obesity. We developed an analytical method to qualify the early-phase insulin secretion; that is, we measured C-peptide immunoreactivity (CPR) response to a selective increase in blood glucose level in portal vein during oral glucose load under a euglycemic hyperinsulinemic clamp (clamp-OGL). Glucose infusion rate, hepatic glucose uptake, and CPR response during clamp-OGL were measured in 30 subjects with diabetes who were divided into 3 groups based on body mass index, 13 obese subjects with normal glucose tolerance (O-NGT), 10 obese subjects with impaired glucose tolerance (O-IGT), and 15 healthy subjects. Significant increase in CPR levels at 10 minutes in clamp-OGL compared with those at steady state was observed in healthy subjects and in O-NGT; however, those were small or absent in diabetic patients and in O-IGT. The incremental ratio of CPR was not correlated to the makers of insulin resistance. The early-phase insulin secretion is well maintained in O-NGT; however, early-phase insulin secretion has already been disturbed in obese subjects with glucose intolerance.
Mizuno
Akira
A
Department of Clinical Biology and Medicine, Institute of Health Bioscience, University of Tokushima, Graduate School, Tokushima 770-8503, Japan. mizuno@clin.med.tokushima-u.ac.jp <mizuno@clin.med.tokushima-u.ac.jp>
Arai
Hidekazu
H
Fukaya
Makiko
M
Sato
Mitsuyo
M
Hisami
Yamanaka-Okumura
YO
Takeda
Eiji
E
Doi
Toshio
T
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin