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      Hepatic and Whole-Body Insulin Metabolism during Proestrus and Estrus in Mongrel Dogs

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          Abstract

          Insulin resistance occurs during various stages of the estrus cycle in dogs. To quantify the effects of proestrus–estrus (PE) and determine whether PE affects liver insulin sensitivity, 11 female mongrel dogs were implanted with sampling and intraportal infusion catheters. Five of the dogs (PE group) entered proestrus after surgery; those remaining in anestrus were controls. The dogs were fasted overnight, [3- 3H]glucose and somatostatin were infused through peripheral veins, and glucagon was infused intraportally. Insulin was infused intraportally, with the rate adjusted to maintain arterial plasma glucose at basal levels (PE, 294 ± 25 µU/kg/min; control, 223 ± 21 µU/kg/min). Subsequently the insulin infusion rate was increased by 0.2 mU/kg/min for 120 min (P1) and then to 1.5 mU/kg/min for the last 120 min (P2); glucose was infused peripherally as needed to maintain euglycemia. Insulin concentrations did not differ between groups at any time; they increased 3 µU/mL over baseline during P1 and to 3 times baseline during P2. The glucose infusion rate in PE dogs during P2 was 63% of that in control dogs. Net hepatic glucose output and the endogenous glucose production rate declined 40% to 50% from baseline in both groups during P1; during P2, both groups exhibited a low rate of net hepatic glucose uptake with full suppression of endogenous glucose production. The glucose disappearance rate during P1 and P2 was 35% greater in control than PE dogs. Therefore, PE in canines is associated with loss of nonhepatic (primarily muscle) but not hepatic insulin sensitivity.

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          Author and article information

          Journal
          Comp Med
          Comp. Med
          cm
          Comparative Medicine
          American Association for Laboratory Animal Science
          1532-0820
          June 2016
          June 2016
          : 66
          : 3
          : 235-240
          Affiliations
          Departments of [1 ]Pathology, Microbiology, Immunology, and Division of Animal Care
          [2 ]Departments of Molecular Physiology and Biophysics
          [3 ]Diabetes Research and Training Center
          [4 ]Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
          Author notes
          [* ]Corresponding author. Email: genie.moore@ 123456vanderbilt.edu
          Article
          PMC4907533 PMC4907533 4907533 2016000235
          4907533
          27298249
          4d73e899-f1ec-44af-ad21-53fe813e8b39
          © American Association for Laboratory Animal Science
          History
          : 14 August 2015
          : 11 October 2015
          : 22 October 2015
          Page count
          Pages: 6
          Categories
          Canine Model

          P2, high-dose hyperinsulinemic clamp period (120–240 min),NEFA, nonesterified fatty acids,P1, low-dose hyperinsulinemic clamp period (0–120 min),PE, proestrus and estrus

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