Bromocriptine mesylate improves glucose tolerance and disposal in a high-fat-fed canine model

Am J Physiol Endocrinol Metab. 2020 Jul 1;319(1):E133-E145. doi: 10.1152/ajpendo.00479.2019. Epub 2020 May 27.

Abstract

Bromocriptine mesylate treatment was examined in dogs fed a high fat diet (HFD) for 8 wk. After 4 wk on HFD, daily bromocriptine (Bromo; n = 6) or vehicle (CTR; n = 5) injections were administered. Oral glucose tolerance tests were performed before beginning HFD (OGTT1), 4 wk after HFD began (Bromo only), and after 7.5 wk on HFD (OGTT3). After 8 wk on HFD, clamp studies were performed, with infusion of somatostatin and intraportal replacement of insulin (4× basal) and glucagon (basal). From 0 to 90 min (P1), glucose was infused via peripheral vein to double the hepatic glucose load; and from 90 to 180 min (P2), glucose was infused via the hepatic portal vein at 4 mg·kg-1·min-1, with the HGL maintained at 2× basal. Bromo decreased the OGTT glucose ΔAUC0-30 and ΔAUC0-120 by 62 and 27%, respectively, P < 0.05 for both) without significantly altering the insulin response. Bromo dogs exhibited enhanced net hepatic glucose uptake (NHGU) compared with CTR (~33 and 21% greater, P1 and P2, respectively, P < 0.05). Nonhepatic glucose uptake (non-HGU) was increased ~38% in Bromo in P2 (P < 0.05). Bromo vs. CTR had higher (P < 0.05) rates of glucose infusion (36 and 30%) and non-HGU (~40 and 27%) than CTR during P1 and P2, respectively. In Bromo vs. CTR, hepatic 18:0/16:0 and 16:1/16:0 ratios tended to be elevated in triglycerides and were higher (P < 0.05) in phospholipids, consistent with a beneficial effect of bromocriptine on liver fat accumulation. Thus, bromocriptine treatment improved glucose disposal in a glucose-intolerant model, enhancing both NHGU and non-HGU.

Keywords: dopamine D2 receptor; glucose tolerance; hypercaloric diet; liver.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Bromocriptine / pharmacology*
  • Diet, High-Fat*
  • Dogs
  • Dopamine Agonists / pharmacology*
  • Fatty Acids, Nonesterified / metabolism
  • Glucagon / drug effects
  • Glucagon / metabolism
  • Glucose / metabolism
  • Glucose Clamp Technique
  • Glucose Intolerance / metabolism*
  • Glucose Tolerance Test
  • Glycogen / metabolism
  • Hepatic Veins
  • Insulin / metabolism
  • Lactic Acid / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Portal Vein
  • Somatostatin

Substances

  • Blood Glucose
  • Dopamine Agonists
  • Fatty Acids, Nonesterified
  • Insulin
  • Lactic Acid
  • Bromocriptine
  • Somatostatin
  • Glycogen
  • Glucagon
  • Glucose