Peripheral glucose metabolism in human hyperprolactinaemia

Foss, Milton César; Paula, Francisco José Albuquerque de; Paccola, G M G F; Piccinato, Carlos Eli

doi:10.1111/j.1365-2265.1995.tb00541.x

Cited by 61 publications

(31 citation statements)

References 23 publications

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“…These elevated plasma prolactin levels are generally 2-4-fold greater than normal and do not constitute frank clinical hyperprolactinemia and would not generally even be assessed as elevated by clinical laboratory standards. However, this relatively elevated plasma prolactin level has been taken as an index of reduced dopaminergic tone at this time of day and several studies have associated high plasma prolactin levels with obesity and insulin resistance in man [150][151][152][153][154][155][156][157][158][159]. Therefore, available evidence in humans supports the tenet that a decreased circadian peak in central (hypothalamic) dopaminergic activity is coupled to the insulin-resistant state, much the same as is observed in other vertebrate animals.…”

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

confidence: 50%

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

confidence: 50%

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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“…The effects of prolactin on β-cell proliferation and insulin production are direct and well established [38, 39]. Moreover, the glucose intolerance in human hyperprolactinemia is thought to be attributable to a reduction in peripheral insulin sensitivity [40, 41]. Although all prolactinoma patients with normal pituitary function enrolled in our study show normoprolactinemia after surgical or medical therapy, it remains to be seen whether insulin secretion is increased in those patients.…”

Section: Discussionmentioning

confidence: 68%

Acylated Ghrelin Secretion Is Acutely Suppressed by Oral Glucose Load or Insulin-Induced Hypoglycemia Independently of Basal Growth Hormone Secretion in Humans

Kim

Kim²,

Shin³

et al. 2006

Horm Res Paediatr

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Background: Ghrelin has been reported to be the natural ligand of growth hormone (GH) secretagogue receptor, and it is known that exogenous ghrelin administration strongly stimulates GH release in humans. However, the effects of endogenous ghrelin on GH secretion and changes in ghrelin levels during dynamic changes in GH levels are not well understood. Methods: Therefore, we measured circulating acylated ghrelin concentrations during oral glucose tolerance tests (OGTTs) in patients with active acromegaly (AA, n = 9) and in age/sex/BMI-matched group A controls (n = 12), and during insulin tolerance testing (ITT) in patients with GH deficiency (GHD, n = 10) and in group B controls (n = 10). Plasma acylated ghrelin, serum GH, insulin and glucose levels were measured during each test. Results: Fasting plasma ghrelin levels correlated negatively with serum insulin levels in both group A and B controls (r = –0.665; p < 0.05) but not in patients with AA or GHD. During OGTTs, circulating ghrelin levels decreased significantly with a nadir at 30 min in both patients with AA (p < 0.05) and group A controls (p < 0.01). Also, ITTs were followed by a significant decrease in circulating ghrelin levels with a nadir at 30 min in patients with GHD (p < 0.05) and in group B controls (p < 0.05). Conclusion: The results of the study show that at baseline acylated ghrelin levels do not differ with respect to the GH status (GH excess or GH deficiency) and, furthermore, the suppression of acylated ghrelin levels during OGTT or ITT is independent of the GH response to the tests.

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“…In rats and humans, PRL increases β-cell proliferation, insulin gene transcription and glucose-dependent insulin secretion [73,74,75,76]. In men and women with chronic hyperprolactinemia, post-prandial hyperinsulinemia and exaggerated insulin secretory response to glucose have been demonstrated [77,78,79]. Interestingly, pancreatic β cells also express dopamine receptors and treatment with the selective D 2 R agonist quinpirole causes the inhibition of glucose-stimulated insulin secretion [80].…”

Section: Discussionmentioning

confidence: 99%

Effect of Cabergoline on Metabolism in Prolactinomas

Auriemma¹,

Granieri²,

Galdiero³

et al. 2013

Neuroendocrinology

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Introduction: Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. Patients and Methods: 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. Results: Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022). Conclusions: CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB.

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Peripheral glucose metabolism in human hyperprolactinaemia

Cited by 61 publications

References 23 publications

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

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

Acylated Ghrelin Secretion Is Acutely Suppressed by Oral Glucose Load or Insulin-Induced Hypoglycemia Independently of Basal Growth Hormone Secretion in Humans

Effect of Cabergoline on Metabolism in Prolactinomas

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