Effect of increased pancreatic islet norepinephrine, dopamine and serotonin concentration on insulin secretion in the Golden hamster

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.

Section: Discussionmentioning

confidence: 99%

Effect of Cabergoline on Metabolism in Prolactinomas

Auriemma¹,

Granieri²,

Galdiero³

et al. 2013

“…With reference to this last point, it is noteworthy that some authors, as for example Zern et al [21], raised the possibility that intracellular monoamines may play a sig nificant role in the regulation o f insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Investigation of Tyrosine-Hydroxylase in the Islets of Langerhans of Adult Mice, Rats and Guinea Pigs

Iturriza

Thibault²

1993

As an indirect way to establish whether catecholamines are actually elaborated in the islets of Langerhans of adult albino and pigmented mice and guinea pigs, or albino rats, the presence of tyrosine-hydroxylase was immunohisto-chemically investigated using a highly specific polyclonal serum against the enzyme. The antiserum was applied to paraffin sections of pancreases fixed either in acrolein or Bouin’s fluid. Such sections were then treated with the avidin-biotin method. Tyrosine-hydroxylase was found exclusively in the β cells of rats and in those of the two strains of mice. Results in the guinea pig varied according to whether the animals were pigmented or albino. In pigmented specimens, the enzyme was detected in β and non-β cells, whereas in albino animals it was undetectable in any of the islet cells. All these observations were performed in material fixed in acrolein. Bouin’s fluid resulted a rather poor fixative for the detection of the enzyme in the islets. The results are compared with those of other authors who investigated the presence of monoamines in the islets of Langerhans. Since tyrosine-hydroxylase is a specific marker for catecholamine-synthesizing cells, it is concluded that insular cells have the ability to elaborate these substances.

“…In rodents, L -DOPA injection results in the accumulation of dopamine in pancreatic β cells and an inhibitory action on insulin response to different secretagogues [60,61], whilst in male rats treated with a dopamine antagonist, high glucose and insulin levels were observed [62]. Insulin secretion is primarily controlled by metabolism-secretion coupling, and is mainly regulated by glucose, but this process can be modulated by the central nervous system through parasympathetic and sympathetic nerves [63].…”

Section: D2rs and Glucose Metabolismmentioning

confidence: 99%

New Insights into the Endocrine and Metabolic Roles of Dopamine D2 Receptors Gained from the <i>Drd2</i><sup>–/–</sup> Mouse

García-Tornadú

Millán²,

Recouvreux³

et al. 2010

Dopamine D2 receptor (D2R) participation in prolactin regulation is well documented, but the role of D2Rs in the control of other hormones involved in growth, food intake and glucose metabolism has not been extensively studied. The study of D2R knockout mice (Drd2^–/–) puts forward new insights into the role of the D2R in growth hormone (GH)-releasing hormone-GH regulation, peptides involved in food intake, glucose homeostasis, as well as in prolactinoma development. The expected phenotype of chronic hyperprolactinemia and prolactinoma development was found in the Drd2^–/– mouse, and this model constitutes a valuable tool in the study of dopamine-resistant prolactinomas. Unexpectedly, these mice were growth retarded, and the importance of functional hypothalamic D2Rs in the neonatal period was revealed. In the Drd2^–/– mouse there was a failure of high neonatal GH levels and therefore the expansion of pituitary somatotropes was permanently altered. These mice also had increased food intake, and a sexually dimorphic participation of the D2R in food intake regulation is suggested. The effect described is probably secondary to D2R regulation of prolactin secretion. Furthermore, the negative modulation of D2Rs on α-melanocyte-stimulating hormone release and positive action on the hypothalamic expression of orexins reveals the complex D2R regulation of food intake. Finally, pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development in the Drd2^–/– mouse may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. These results highlight the complex endocrine actions of the D2Rs at different levels, hypothalamus, pituitary or pancreas, which function to improve fitness, reproductive success and survival.