Bromocriptine inhibits the seasonally occurring obesity, hyperinsulinemia, insulin resistance, and impaired glucose tolerance in the Syrian hamster, Mesocricetus auratus

Cincotta, Anthony H.; Schiller, B; Meier, Albert

doi:10.1016/0026-0495(91)90057-4

Cited by 76 publications

(71 citation statements)

References 42 publications

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“…Two weeks of bromocriptine treatment reduced body weight (from 223.4g to 210.4g, P < 0.02), while the weight of the vehicle treated animals remained the same (from 222.6g to 221.9g, P = 0.9), to produce a between group difference in change from baseline body weight of -12.3g (P < 0.001) without altering food consumption (11.0g vs. 10.3g per day, P = 0.3) as has been repeatedly reported in these animals [1][2][3].…”

Section: Resultssupporting

confidence: 63%

“…Body weight and food consumption were recorded during the treatment stage. Such animals of this age, sex and photoperiod exposure have been established to be severely insulin resistant and glucose intolerant [1,2,15]. Animal maintenance and all experimental procedures were conducted in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals.…”

Section: Animals and Diet Protocolmentioning

confidence: 99%

“…Timed daily systemic or intracerebroventricular administration of bromocriptine, a dopamine D2 receptor agonist, to hyperinsulinemic, insulin resistant animals or once daily (morning) systemic administration of bromocriptine-QR, a quick release formulation of bromocriptine to such humans improves fasting hyperinsulinemia and impaired glucose tolerance by simultaneously reducing post glucose challenge plasma glucose and insulin levels [1][2][3][4]. However in these studies, fasting plasma glucose reductions in response to such treatment varied from not at all to moderate depending upon the prevailing glucose level.…”

Section: Introductionmentioning

confidence: 99%

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Weighted Effects of Bromocriptine Treatment on Glucose Homeostasis during Hyperglycemic versus Euglycemic Clamp Conditions in Insulin Resistant Hamsters: Bromocriptine as a Unique Postprandial Insulin Sensitizer

Ezrokhi¹,

Luo²,

Trubitsyna³

et al. 2012

J Diabetes Metab

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Background: Postprandial glucose metabolism is deranged in insulin resistant states typified by increased hepatic glucose output and reduced peripheral and hepatic glucose deposition despite elevated plasma insulin levels. And, mounting evidence suggests that postprandial hyperglycemia may potentiate cardiovascular disease. Time-of-day pulsed bromocriptine (a dopamine D2 receptor agonist) administration to insulin resistant animals and humans improves impaired glucose tolerance and post-meal hyperglycemia without raising the plasma insulin level when assayed many hours after bromocriptine has been removed from the circulation. The bromocriptine response of glucose lowering is more prominent after a meal than just before the meal suggesting a "weighted" effect on postprandial glucose metabolism. However, this supposition has never been evaluated under controlled physiological glucose-insulin clamp conditions to verify the existence of such a unique phenomenon. Findings:This study therefore investigated the effects of daily bromocriptine or vehicle administration for 2 weeks on hepatic glucose output and total body glucose disposal during such hyperglycemic versus euglycemic insulin clamp conditions in insulin resistant, glucose intolerant Syrian hamsters. Bromocriptine treatment improved fasting insulin sensitivity (HOMA-IR) by 38% P < 0.04 and both total body glucose disposal and hepatic glucose output during the euglycemic clamp by 21% and 26%, P < 0.03 respectively, relative to vehicle treated animals. Importantly, the incremental increase in total body glucose disposal and inhibition in hepatic glucose output under hyperglycemic versus euglycemic conditions was greater (73% vs. 40%, P < 0.001) and markedly stronger (30% vs. no change, P < 0.002), respectively, in bromocriptine versus vehicle treated animals, respectively. Conclusions:These findings indicate a unique hyperglycemic environment "weighted" effect of bromocriptine on improving glucose homeostasis in insulin resistant animals that is independent of plasma insulin level.

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Section: Resultssupporting

confidence: 63%

Section: Animals and Diet Protocolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Weighted Effects of Bromocriptine Treatment on Glucose Homeostasis during Hyperglycemic versus Euglycemic Clamp Conditions in Insulin Resistant Hamsters: Bromocriptine as a Unique Postprandial Insulin Sensitizer

Ezrokhi¹,

Luo²,

Trubitsyna³

et al. 2012

J Diabetes Metab

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“…Moreover, numerous studies have consistently demonstrated the ability of such circadian-timed daily administration of bromocriptine (systemic or intracerebroventricular) to markedly reduce insulin resistance (particularly during the postprandial state [125,126], in agreement with its ability to improve VMH hypothalamic fuel-sensing mechanisms as described above), hyperinsulinemia and/or glucose intolerance without raising the plasma insulin level, in a variety of animal models of IRS including seasonal insulin-resistant hamsters, SHRs, high-fat fed rats, genetically leptin-deficient ob/ob mice, fattened pigs, and high-fat fed dogs [86,124,[126][127][128][129][130][131][132]. As a composite, these animal studies provide evidence that timed bromocriptine treatment improves dysglycemia by improving (postprandial) insulin action in the liver and/or peripheral insulin-sensitive tissues (e.g.…”

Section: Non-scn Cns Dopaminergic Activities Regulating Peripheral Mementioning

confidence: 80%

“…Such timed bromocriptine treatment also markedly reduced basal and insulin-stimulated hepatic lipogenesis, hepatic triglyceride (TG) secretion, and plasma TG level during the circadian peak of hepatic lipogenic responsiveness to insulin in insulin-resistant hamsters [134,135]. Bromocriptine therapy also reduced total body fat stores and hepatic lipid content in animal models of obesity and fatty liver disease (high-saturated fat diet fed rats, SHRs) [86,131].…”

Section: Non-scn Cns Dopaminergic Activities Regulating Peripheral Mementioning

confidence: 99%

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

Raskin

Cincotta

2016

Expert Review of Endocrinology & Metabolism

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An extended series of studies indicate that endogenous phase shifts in circadian neuronal input signaling to the biological clock system centered within the hypothalamic suprachiasmatic nucleus (SCN) facilitates shifts in metabolic status. In particular, a diminution of the circadian peak in dopaminergic input to the peri-SCN facilitates the onset of fattening, insulin resistance and glucose intolerance while reversal of low circadian peak dopaminergic activity to the peri-SCN via direct timed dopamine administration to this area normalizes the obese, insulin resistant, glucose intolerant state in high fat fed animals. Systemic circadian-timed daily administration of a potent dopamine D2 receptor agonist, bromocriptine, to increase diminished circadian peak dopaminergic hypothalamic activity across a wide variety of animal models of metabolic syndrome and type 2 diabetes mellitus (T2DM) results in improvements in the obese, insulin resistant, glucose intolerant condition by improving hypothalamic fuel sensing and reducing insulin resistance, elevated sympathetic tone, and leptin resistance. A circadian-timed (within 2 hours of waking in the morning) once daily administration of a quick release formulation of bromocriptine (bromocriptine-QR) has been approved for the treatment of T2DM by the U.S. Food and Drug Administration. Clinical studies with such bromocriptine-QR therapy (1.6 to 4.8 mg/day) indicate that it improves glycemic control by reducing postprandial glucose levels without raising plasma insulin. Across studies of various T2DM populations, bromocriptine-QR has been demonstrated to reduce HbA1c by -0.5 to -1.7. The drug has a good safety profile with transient mild to moderate nausea, headache and dizziness as the most frequent adverse events noted with the medication. In a large randomized clinical study of T2DM subjects, bromocriptine-QR exposure was associated with a 42% hazard ratio reduction of a pre-specified adverse cardiovascular endpoint including myocardial infarction, stroke, hospitalization for congestive heart failure, revascularization surgery, or unstable angina. Bromocriptine-QR represents a novel method of treating T2DM that may have benefits for cardiovascular disease as well. ARTICLE HISTORY

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Bromocriptine for type 2 diabetes mellitus

Ooi

Loke

2013

Cochrane Database of Systematic Reviews

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Bromocriptine inhibits the seasonally occurring obesity, hyperinsulinemia, insulin resistance, and impaired glucose tolerance in the Syrian hamster, Mesocricetus auratus

Cited by 76 publications

References 42 publications

Weighted Effects of Bromocriptine Treatment on Glucose Homeostasis during Hyperglycemic versus Euglycemic Clamp Conditions in Insulin Resistant Hamsters: Bromocriptine as a Unique Postprandial Insulin Sensitizer

Weighted Effects of Bromocriptine Treatment on Glucose Homeostasis during Hyperglycemic versus Euglycemic Clamp Conditions in Insulin Resistant Hamsters: Bromocriptine as a Unique Postprandial Insulin Sensitizer

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

Bromocriptine for type 2 diabetes mellitus

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