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

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 ΔAUC0–30and ΔAUC0–120by 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.