Extrapancreatic action of truncated glucagon-like peptide-I in Otsuka Long-Evans Tokushima Fatty rats, an animal model for non-insulin-dependent diabetes mellitus.
To clarify the mechanism(s) of the antidiabetic effects of truncated glucagon-like peptide-1 (GLP-1) in diabetics, we examined its insulinotropic and extrapancreatic effects in a newly established strain of spontaneously non-insulin-dependent diabetic (NIDDM) rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, that received a continuous infusion of truncated GLP-1 620 pmol/d/kg (G group, n = 12) or of vehicle (V group, n = 12) for 4 weeks by Alzet pump. Nonfasting plasma glucose levels were significantly lower (P < .05) in the G group than in the V group (7.0 +/- 0.67 v 9.1 +/- 1.7 mmol/L), and fasting plasma immunoreactive insulin (IRI) levels were lower in the former than in the latter (0.63 +/- 0.31 v 0.78 +/- 0.25 nmol/L). At day 15 of infusion, the G group showed an attenuated plasma glucose response to an oral glucose load, but had plasma IRI levels comparable to those in the V group. A long-term infusion of truncated GLP-1 increased the glucose infusion rate (GIR) significantly (P < .05) during a euglycemic-hyperinsulinemic clamp test (59.0 +/- 14.8 mumol/kg/min for group G v 38.9 +/- 12.2 for group V), but hepatic glucose output (HGO) did not differ significantly for either group. Uptake of 2-deoxy-D-glucose (2DG) by peripheral muscles in the G group was as much as 2.4-fold higher than in the V group (5.52 +/- 2.04 v 2.29 +/- 0.97 mumol/100 g muscle weight/min). We conclude from these data that truncated GLP-1, in addition to its well-known incretin effect, is capable of augmenting insulin action in peripheral tissues of diabetics, which can contribute, in part, to improve glucose intolerance in OLETF rats.
Mizuno
A
A
Department of Laboratory Medicine, School of Medicine, University of Tokushima, Japan.
Kuwajima
M
M
Ishida
K
K
Noma
Y
Y
Murakami
T
T
Tateishi
K
K
Sato
I
I
Shima
K
K
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000494:pharmacology; D007260:Infusion Pumps; D007328:Insulin / Q000097:blood; D008297:Male; D010179:Pancreas / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose