Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kim, SP; Ellmerer, M; Kirkman, EL; Bergman, RN.
Beta-cell rest accompanies reduced first-pass hepatic insulin extraction in the insulin-resistant, fat-fed canine model.
Am J Physiol Endocrinol Metab. 2007; 292(6):E1581-E1589
Doi: 10.1152/ajpendo.00351.2006
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- Co-Autor*innen der Med Uni Graz
- Ellmerer Martin
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- Abstract:
- During insulin resistance, glucose homeostasis is maintained by an increase in plasma insulin via increased secretion and/or decreased first-pass hepatic insulin extraction. However, the relative importance of insulin secretion vs. clearance to compensate for insulin resistance in obesity has yet to be determined. This study utilizes the fat-fed dog model to examine longitudinal changes in insulin secretion and first-pass hepatic insulin extraction during development of obesity and insulin resistance. Six dogs were fed an isocaloric diet with an approximately 8% increase in fat calories for 12 wk and evaluated at weeks 0, 6, and 12 for changes in 1) insulin sensitivity by euglycemic-hyperinsulinemic clamp, 2) first-pass hepatic insulin extraction by direct assessment, and 3) glucose-stimulated insulin secretory response by hyperglycemic clamp. We found that 12 wk of a fat diet increased subcutaneous and visceral fat as assessed by MR imaging. Consistent with increased body fat, the dogs exhibited a approximately 30% decrease in insulin sensitivity and fasting hyperinsulinemia. Although insulin secretion was substantially increased at week 6, beta-cell sensitivity returned to prediet levels by week 12. However, peripheral hyperinsulinemia was maintained because of a significant decrease in first-pass hepatic insulin extraction, thus maintaining hyperinsulinemia, despite changes in insulin release. Our results indicate that when obesity and insulin resistance are induced by an isocaloric, increased-fat diet, an initial increase in insulin secretion by the beta-cells is followed by a decrease in first-pass hepatic insulin extraction. This may provide a secondary physiological mechanism to preserve pancreatic beta-cell function during insulin resistance.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipose Tissue - pathology
- Animals - pathology
- Body Composition - pathology
- Dietary Fats - administration and dosage
- Dogs - administration and dosage
- Fasting - blood
- Glucose Clamp Technique - blood
- Hyperinsulinism - etiology
- Insulin - metabolism
- Insulin Resistance - metabolism
- Insulin-Secreting Cells - secretion
- Liver - metabolism
- Magnetic Resonance Imaging - metabolism
- Male - metabolism
- Obesity - diagnosis
- Find related publications in this database (Keywords)
- hyperinsulinemia
- insulin resistance
- obesity
- insulin secretion
- insulin clearance