Central Prolactin Modulates Insulin Sensitivity and Insulin Secretion in Diabetic Rats

Park, Sunmin; Kang, Suna; Lee, Hye Won; Ko, Byoung‐Seob

doi:10.1159/000336501

Cited by 43 publications

(40 citation statements)

References 54 publications

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“…These mice had reductions in pancreatic islet density and β cell mass, together with blunted insulin secretory responses to glucose compared with wild-type littermates [40]. Physiologically elevated prolactin levels induce normal adaptive processes, including expansion of the β cell mass and improvements in hepatic insulin sensitivity, that ultimately increase glucose-stimulated insulin secretion in diabetic rats [41]. Animal and human studies have clearly shown that the β cell mass influences the insulin secretory capacity and the risk of developing T2DM [42,43]…”

Section: Mechanisms Underlying the Possible Protective Effects Of Brementioning

confidence: 99%

Beneficial effects of breastfeeding in women with gestational diabetes mellitus

Much

Beyerlein

Rossbauer

et al. 2014

Molecular Metabolism

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Gestational diabetes mellitus (GDM) increases the future risk of developing type 2 diabetes mellitus (T2DM). There is now a growing evidence that breastfeeding has short- and long-term health benefits for mothers with GDM. Mothers with GDM who breastfeed have improved lipid and glucose metabolic profiles for the first 3 months after birth. However, women with GDM are less likely to breastfeed and, if they do, breastfeeding is usually continued for a shorter duration compared with women without GDM. One long-term prospective study followed women with GDM from delivery for up to 19 years postpartum, and found that breastfeeding for ≥3 months reduced the risk of T2DM and delayed the development of T2DM by a further 10 years compared with breastfeeding for <3 months. However, the physiological mechanisms underlying the protective effects of breastfeeding are still unknown, even though it is important to gain a full understanding of the pathways involved in these effects. Therefore, the purpose of this review is to provide a comprehensive analysis of the recent developments in the field of GDM and breastfeeding. We reviewed data from animal experiments and human studies. We also provide insight into the molecular pathways and describe promising topics for future research.

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Section: Mechanisms Underlying the Possible Protective Effects Of Brementioning

confidence: 99%

Beneficial effects of breastfeeding in women with gestational diabetes mellitus

Much

Beyerlein

Rossbauer

et al. 2014

Molecular Metabolism

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“…In normal healthy humans, plasma prolactin concentrations peak at night during sleep and are relatively low during the wakeful daylight period of the day (reviewed in [50]), and animal studies indicate this inhibition is due in large part to inhibition from hypothalamic dopaminergic tone [146]. Generally, a large fraction of obese, insulin-resistant humans have diurnal (day-time) plasma prolactin levels that are elevated relative to lean, insulin-sensitive subjects [147][148][149][150][151].…”

Section: Clinical Effects Of Bromocriptine-qr Therapy In the Treatmenmentioning

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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“…The possible explanations for this association were provided by experimental studies showing that mild increases in prolactin levels and placental lactogens during pregnancy determined the increase in beta cell mass and glucose-stimulated insulin secretion [38,39], these modifications being essential to the maintenance of normal glucose metabolism in pregnancy. Moreover, in rats, both intracerebroventricular and intraperitoneal infusions of a low dose of prolactin resulted in a mild increase in circulating prolactin, determining the enhancement of insulin secretion and improvement in insulin sensitivity [40,41]. Indeed, our data showed associations of higher prolactin levels within normal ranges of lower fasting insulin and HOMA-IR values in bivariate analysis.…”

Section: Discussionmentioning

confidence: 49%

Is prolactin the missing link in adipose tissue dysfunction of polycystic ovary syndrome patients?

Albu

Florea²,

Fica

2015

Endocrine

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The aims of the study were to evaluate whether adiposity was among the determinants of circulating prolactin levels and to determine whether serum prolactin independently predicted metabolic abnormalities in patients with polycystic ovary syndrome (PCOS). A total of 322 PCOS patients with normal serum prolactin levels were recruited between January 2007 and January 2014. Anthropometric, metabolic, and hormonal parameters were measured in all of the patients. HOMA-IR was calculated as an index of insulin resistance. Serum prolactin was negatively correlated with age (p < 0.0001), all the adiposity indices [body mass index p < 0.0001; waist circumference p < 0.0001; waist-hip ratio (WHR) p < 0.0001], visceral adiposity index (VAI, p = 0.043), fasting insulinemia (p = 0.002), and HOMA-IR (p = 0.002), and was positively correlated with serum adiponectin (p = 0.034), but not with circulating androgens or serum leptin levels. Serum adiponectin, but not HOMA-IR or fasting insulinemia, was independently associated with serum prolactin after adjustment for age, leptin, and anthropometrical adiposity parameters. Of the adiposity parameters, only WHR and VAI were independent predictors of serum prolactin after adjustment for adiponectin. Circulating prolactin was also negatively correlated with fasting glycemia (only in patients with normal glucose metabolism, p = 0.037) and was inversely correlated with the presence of metabolic syndrome (p < 0.001), but this association was not maintained after adjustment for possible confounders. In PCOS patients, serum prolactin level was related to adipose tissue quantity and function, and adiponectin was a possible mediator of this relationship. Low serum prolactin levels were associated with an unfavorable metabolic profile, but this association seemed to be due to the complex interplay among prolactin, adiposity, and insulin resistance rather than to a direct metabolic effect of prolactin.

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Central Prolactin Modulates Insulin Sensitivity and Insulin Secretion in Diabetic Rats

Cited by 43 publications

References 54 publications

Beneficial effects of breastfeeding in women with gestational diabetes mellitus

Beneficial effects of breastfeeding in women with gestational diabetes mellitus

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

Is prolactin the missing link in adipose tissue dysfunction of polycystic ovary syndrome patients?

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