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Bromocriptine Mesylate Improves Glucose Tolerance and Disposal in a High-Fat-Fed
Moore MC, Smith MS, Swift LL, Cincotta AH, Ezrokhi M, Cominos N, Zhang Y, Farmer
B, Cherrington AD
Submitted Externally on 5/28/2020
American journal of physiology. Endocrinology and metabolism
Volume : Pages
Bromocriptine mesylate treatment was examined in dogs fed a high fat diet (HFD)
for 8 weeks. After 4 weeks 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 weeks after HFD began (Bromo only),
and after 7.5 weeks on HFD (OGTT3). After 8 weeks on HFD, clamp studies were
performed, with infusion of somatostatin and intraportal replacement of insulin
(4xbasal) and glucagon (basal). From 0-90 min (P1), glucose was infused via
peripheral vein to double the hepatic glucose load (HGL); and from 90-180 min
(P2), glucose was infused via the hepatic portal vein at 4 mg·kg-1·min-1, with
the HGL maintained at 2xbasal. Bromo decreased the OGTT glucose ?AUC0-30 and
?AUC0-120 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 (nonHGU) 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 nonHGU (~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 nonHGU.
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Financial support for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
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