期刊
JOURNAL OF APPLIED PHYSIOLOGY
卷 110, 期 2, 页码 458-467出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00768.2010
关键词
hyperinsulinemic euglycemic clamp; insulin resistance; oral glucose tolerance; pancreatic islet; pregnancy
资金
- American Diabetes Association [7-06-RA-96]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK071052, DK20593]
- Juvenile Diabetes Research Foundation (JDRF) [1-2007-548, 3-2009-153]
- Vanderbilt Diabetes Research and Training Center Metabolic Physiology Shared Resource and Hormone Assay & Analytical Services Cores
Glucose metabolism was compared in dogs consuming a chow/meat diet throughout pregnancy (P group, n = 6) and dogs switched to a high-fat/high-fructose (HFF) diet during the 4th-5th gestational week (gestation similar or equal to 9 wk; P-HFF group; n = 6). An oral glucose tolerance test (OGTT; 0.9 g/kg) was administered in the 6th-7th gestational week, and a hyperinsulinemic [0-120 min: 1.8 pmol,kg(-1).min(-1) (low insulin); 120-240 min: 9 pmol.kg(-1).min(-1) (high insulin)] euglycemic clamp was performed the following week. Nonpregnant (NP) female dogs underwent OGTTs but not clamp studies. All P-HFF dogs exhibited impaired glucose tolerance (IGT) or gestational diabetes (GDM), but only one P dog had IGT. Insulin concentrations in P and P-HFF dogs were significantly lower than in NP dogs 30 and 60 min after the OGTT. Therefore, mean islet size and area were evaluated in P and NP dogs. These values did not differ between groups, and proliferating endocrine cells were rare in pregnancy. During exposure to high insulin, glucose infusion rate and hindlimb glucose uptake were similar to 30% greater (P < 0.05) and net hepatic glucose output was more suppressed (-5.5 +/- 6.1 vs. 7.8 +/- 2.8 mg,100 g liver(-1).min(-1), P < 0.05) in P than in P-HFF dogs. In conclusion, in the 2nd trimester the canine pancreas does not exhibit islet hypertrophy, hyperplasia, or neogenesis. Combined with the lack of pancreatic adaptation, a HFF diet during late pregnancy produces a canine model of IGT and GDM without hyperinsulinemia but exhibiting liver and muscle insulin resistance.
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