J. Rachman et al., NORMALIZATION OF INSULIN RESPONSES TO GLUCOSE BY OVERNIGHT INFUSION OF GLUCAGON-LIKE PEPTIDE-1(7-36) AMIDE IN PATIENTS WITH NIDDM, Diabetes, 45(11), 1996, pp. 1524-1530
Citations number
40
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Glucagon-like peptide 1 (GLP-1) is a natural enteric incretin hormone,
which is a potent insulin secretogogue in vitro and in vivo in humans
. Its effects on overnight glucose concentrations and the specific pha
ses of insulin response to glucose and nonglucose secretogogues in sub
jects with NIDDM are not known. We compared the effects of overnight i
ntravenous infusion of GLP-1 (7-36) amide with saline infusion, on ove
rnight plasma concentrations of glucose, insulin, and glucagon in eigh
t subjects with NIDDM. The effects on basal (fasting) beta-cell functi
on and insulin sensitivity were assessed using homeostasis model asses
sment (HOMA) and compared with seven age- and weight-matched nondiabet
ic control subjects. The GLP-1 infusion was continued, and the first-
and second-phase insulin responses to a 2-h 13 mmol/l hyperglycemic cl
amp and the insulin response to a subsequent bolus of tile nonglucose
secretogogue, arginine, were measured. These were compared with simila
r measurements recorded after the overnight saline infusion and in the
control subjects who were not receiving GLP-1. The effects on stimula
ted beta-cell function of lowering plasma glucose per se were assessed
by a separate overnight infusion of soluble insulin, the rate of whic
h was adjusted to mimic the blood glucose profile achieved with GLP-1.
Infusion of GLP-1 resulted in significant lowering of overnight plasm
a concentrations compared with saline, with postabsorptive glucose con
centrations (2400-0800) of 5.6 +/- 0.8 and 7.8 +/- 1.4 mmol/l, respect
ively (P < 0.0002). Basal beta-cell function assessed by HOMA was impr
oved from geometric mean (1 SD range), 45% beta (24-85) to 91% beta (5
5-151) by GLP-1 (P < 0.0004). First-phase incremental insulin response
to glucose was improved by GLP-1 from 8 pmol/l (-8-33) to 116 pmol/l
(12-438) (P < 0.005), second-phase insulin response to glucose from 13
6 pmol/l (53-352) to 1,156 pmol/l (357-3,748) (P < 0.0002), and increm
ental insulin response to arginine from 443 pmol/l (172-1,144) to 811
pmol/l (272-2,417) (P < 0.002). All responses on GLP-1 were not signif
icantly different from nondiabetic control subjects. Reduction of over
night glucose by exogenous insulin did not improve any of the phases o
f stimulated beta-cell function. Prolonged intravenous infusion of GLP
-1 thus significantly lowered overnight glucose concentrations in subj
ects with NIDDM and improved both basal and stimulated beta-cell funct
ion to nondiabetic levels. It may prove to be a useful agent in the re
duction of hyperglycemia in NIDDM.