Effects of Long-Term L-Dopa Therapy on Carbohydrate Metabolism in Patients with Parkinson’s Disease

Rosati, Gianpaolo; Maioli, M.; Aiello, I.; A, Farris; Agnetti, Virgilio

doi:10.1159/000114744

Cited by 36 publications

(22 citation statements)

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“…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]. In rodents, a single injection with the dopamine precursor L -dopa results in inhibited insulin secretory response [81,82], whereas treatment with L -dopa in humans suffering from Parkinson's disease reduces insulin secretion upon a glucose load [83]. FG and insulin, as well as HOMA-IR, have been found significantly ameliorated also in patients with Cushing's disease following a 24-month treatment with CAB after unsuccessful surgery [84].…”

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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Section: Discussionmentioning

confidence: 99%

Effect of Cabergoline on Metabolism in Prolactinomas

Auriemma¹,

Granieri²,

Galdiero³

et al. 2013

Neuroendocrinology

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“…One can speculate that changes in dopamine levels might generate multiple responses, allowing coordination of feeding behaviors together with regulation of pancreatic endocrine and exocrine functions. Interestingly, treatment with L-dopa alters insulin secretion in patients with Parkinson disease (10,57,58). Moreover, antipsychotic (neuroleptic) drugs blocking dopamine receptors may cause hyperinsulinemia (59), hypoglycemia (60), increase appetite, and obesity (61,62) and are associated with diabetes (61,63,64).…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with dopamine precursor L-dopa in humans suffering from Parkinson disease reduces insulin secretion upon oral glucose tolerance test (10). In rodents, a single injection with L-dopa results in the accumulation of dopamine in beta cells and inhibition of the insulin secretory responses (11,12).…”

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confidence: 99%

Dopamine D2-like Receptors Are Expressed in Pancreatic Beta Cells and Mediate Inhibition of Insulin Secretion

Rubı́

Ljubicic

Pournourmohammadi

et al. 2005

Journal of Biological Chemistry

228

205

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Dopamine is a neurotransmitter that plays a critical role in neurological and psychiatric disorders, such as schizophrenia, Parkinson disease, and drug addiction (1). Increasing evidence also shows implication of dopamine in various physiological functions such as cell proliferation (2), gastrointestinal protection (3), and inhibition of prolactin secretion (4). Effects of dopamine on insulin secretion in general and on pancreatic beta cell function in particular have been poorly studied. Insulin exocytosis from the beta cell is primarily controlled by metabolismsecretion coupling. First, glucose equilibrates across the plasma membrane and is phosphorylated by glucokinase, initiating glycolysis (5). Subsequently, mitochondrial metabolism generates ATP, which promotes the closure of ATP-sensitive potassium channels and, as a consequence, depolarization of the plasma membrane (6). This leads to calcium influx through voltage-gated calcium channels and a rise in cytosolic calcium, triggering insulin exocytosis (6, 7). Additional signals participating in the amplifying pathway (8) are necessary to reproduce the sustained secretion elicited by glucose. Insulin secretion evoked by glucose metabolism can be further modulated by parasympathetic and sympathetic neurotransmitters (9).Treatment with dopamine precursor L-dopa in humans suffering from Parkinson disease reduces insulin secretion upon oral glucose tolerance test (10). In rodents, a single injection with L-dopa results in the accumulation of dopamine in beta cells and inhibition of the insulin secretory responses (11,12). In isolated islets, analogues of dopamine inhibit glucose-stimulated insulin release (13), whereas one study reports potentiation of insulin secretion upon acute dopamine accumulation (14). Taken as a whole, these previous studies suggest that beta cells might be directly responsive to dopamine. Here, we investigated the molecular mechanisms implicated in beta cell responses to dopamine action. In particular, the present data demonstrate the presence of dopamine receptors in beta cells. Moreover, the inhibitory effects of dopamine are predominantly ascribed to activation of the D2-like receptor family members. MATERIALS AND METHODS INS-1E Cells and Pancreatic Islets-INS-1Ecells, used as a well differentiated beta cell clone (15), were cultured in a humidified atmosphere containing 5% CO 2 in a medium composed of RPMI 1640 supplemented with 10 mM Hepes, 5% (v/v) heat-inactivated fetal calf serum, 2 mM glutamine, 100 units/ml penicillin, 100 g/ml streptomycin, 1 mM sodium pyruvate, and 50 M 2-mercaptoethanol. For rodent islets, Wistar rats or BALB/c mice weighing 200 -250 g and 25-30 g, respectively, were obtained from in-house breeding (CMU-Zootechnie, Geneva, Switzerland). We followed the principles of laboratory animal care, and the study was approved by the responsible ethics committee. Pancreatic islets were isolated by collagenase digestion and handpicking from male Wistar rats or BALB/c mice as described previously (16). Isolated islets w...

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“…Sandyk et al [23] reported impaired glucose tolerance in 50-80 % of patients with PD whom they studied and concluded that levodopa treatment aggravated it. Other authors, however, have reported that levodopa did not impair glucose tolerance [22] nor enhance plasma insulin and glucose concentration levels [24]. Davies et al [6] postulated that weight loss in PD patients is due to an increased metabolic rate or altered muscle metabolism.…”

Section: ■ Increased Energy Metabolismmentioning

confidence: 99%

Weight loss in Parkinson’s disease

Kashihara

2006

J Neurol

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Weight loss is frequent in patients with Parkinson's disease (PD). Reduced energy intake and/or increased energy expenditure have been postulated as the cause. Dysphagia, anorexia, and gastrointestinal dysfunction may be possible causes of reduced energy intake; whereas, rigidity, tremor, and levodopa-induced dyskinesia may increase energy expenditure. Levodopa may enhance glucose metabolism resulting in enhanced energy expenditure. Depression, anti-parkinsonian drugs, and medical complications such as pneumonia and malignancies also may facilitate weight loss in PD. Combinations of various degrees of these factors, especially in advanced PD, may produce weight loss. Such weight loss is associated with malnutrition which may precipitate infection and decubitis; accelerate motor, behavioral, and autonomic impairment; consequently spoiling one's quality of life. Attention must be paid as well to motor symptoms to prevent or reverse weight loss in PD patients.

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Effects of Long-Term L-Dopa Therapy on Carbohydrate Metabolism in Patients with Parkinson’s Disease

Cited by 36 publications

References 0 publications

Effect of Cabergoline on Metabolism in Prolactinomas

Effect of Cabergoline on Metabolism in Prolactinomas

Dopamine D2-like Receptors Are Expressed in Pancreatic Beta Cells and Mediate Inhibition of Insulin Secretion

Weight loss in Parkinson’s disease

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