TITLE

Oxyntomodulin Increases Insulin Secretion but Does Not Affect Insulin Sensitivity in High-Fat-Fed C57B1/6 Mice

AUTHOR(S)
Parlevliet, Edwin T.; Heijboer, Annemieke C.; Schröder-Van Der Elst, Janny P.; Havekes, Louis M.; Romijn, Johannes A.; Pijl, Hanno; Corssmit, Eleonora P.
PUB. DATE
June 2007
SOURCE
Diabetes;Jun2007 Supplement 1, Vol. 56, pA373
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Gut-derived peptides like ghrelin and glucagon-like peptide (GLP-1) affect glucose metabolism in many ways, e.g. by altering insulin sensitivity or secretion. The proglucagon-derived peptide oxyntomodulin (OXM) is cosecreted with GLP-1 and inhibits feeding in rodents and man. We evaluated the effects of OXM on glucose metabolism in diet-induced insulin resistant male C57B1/6 mice independent of food intake. To determine effects on glucose tolerance, overnight-fasted mice were intraperitoneally (i.p.) injected with OXM (0.75, 2.5, or 7.5 nmol) or vehicle (n=6/group) followed by an intraperitoneal glucose tolerance test. Glucose turnover rates were determined during a hyper-insulinemic euglycemic clamp with continuous intravenous infusion of 0.75 nmol/h OXM (n=8) in combination with [sup 14]C-glucose infusion. OXM dose-dependently improved glucose tolerance as estimated by the area under the curve (AUC) for glucose (OXM, 7.5 nmol: 1564±460, p<0.01; 2.5 nmol: 1828±684, p<0.01; 0.75 nmol: 2322±303, p<0.05; control: 2790±222). Insulin levels in response to glucose administration were increased in 7.5 nmol OXM-treated animals compared to control (AUC insulin: 343±113 vs. 231±39, p<0.05). OXM significantly enhanced glucose infusion rate (129±41 vs. 39±26 µl/h, p<0.01) and glucose disposal (84±15 vs. 40-±6 µmol/min/kg, p<0.01) during insulin infusion compared to control. Also, insulin's capacity to inhibit glucose production was reinforced by OXM (41±1 vs. 16±13 %inhibition, p<0.01). However, insulin levels were significantly higher in OXM-treated mice compared to control (8.3±3.1 vs. 4.9±2.4 ng/ml, p<0.01). Indeed, if expressed per unit concentration of circulating insulin, glucose production and disposal were not different between groups. We conclude that OXM beneficially affects glucose metabolism in diet-induced insulin resistant C57B1/6 mice. It ameliorates glucose intolerance, most likely through an incretin effect on insulin secretion. OXM does not appear to impact on insulin action.
ACCESSION #
25821756

 

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