Dataset Information

Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy.

ABSTRACT: The past decade has witnessed a revival of interest in the hormone melatonin, partly attributable to the discovery that genetic variation in MTNR1B - the melatonin receptor gene - is a risk factor for impaired fasting glucose and type 2 diabetes (T2D). Despite intensive investigation, there is considerable confusion and seemingly conflicting data on the metabolic effects of melatonin and MTNR1B variation, and disagreement on whether melatonin is metabolically beneficial or deleterious, a crucial issue for melatonin agonist/antagonist drug development and dosing time. We provide a conceptual framework - anchored in the dimension of 'time' - to reconcile paradoxical findings in the literature. We propose that the relative timing between elevated melatonin concentrations and glycemic challenge should be considered to better understand the mechanisms and therapeutic opportunities of melatonin signaling in glycemic health and disease.

SUBMITTER: Garaulet M

PROVIDER: S-EPMC7349733 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy.

Garaulet Marta M Qian Jingyi J Florez Jose C JC Arendt Josephine J Saxena Richa R Scheer Frank A J L FAJL

Trends in endocrinology and metabolism: TEM 20200101 3

The past decade has witnessed a revival of interest in the hormone melatonin, partly attributable to the discovery that genetic variation in MTNR1B - the melatonin receptor gene - is a risk factor for impaired fasting glucose and type 2 diabetes (T2D). Despite intensive investigation, there is considerable confusion and seemingly conflicting data on the metabolic effects of melatonin and MTNR1B variation, and disagreement on whether melatonin is metabolically beneficial or deleterious, a crucial ...[more]

PMID: 31901302

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Project description:Patients with type 2 diabetes mellitus (T2DM) have a higher incidence of cardiovascular (CV) events. The ingestion of high-glycemic index (GI) diets, specially sweetened beverage consumption, has been associated with the development of T2DM and CV disease. We investigated the effects of the intake of a sweetened beverage, obtained from natural carbohydrates containing pinitol (PEB) compared to a sucrose-enriched beverage (SEB) in the context of impaired glucose tolerance (IGT) and diabetes. The study was divided in three different phases: (1) a discovery phase where the plasma proteomic profile was investigated by 2-DE (two-dimensional electrophoresis) followed by mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight-MALDI-TOF/TOF) in healthy and IGT volunteers; (2) a verification phase where the potential mechanisms behind the observed protein changes were investigated in the discovery cohort and in an additional group of T2DM volunteers; and (3) the results were validated in a proof-of-concept interventional study in an animal model of diabetic rats with complementary methodologies. Six weeks of pinitol-enriched beverage (PEB) intake induced a significant increase in two proteins involved in the insulin secretion pathway, insulin-like growth factor acid labile subunit (IGF1BP-ALS; 1.3-fold increase; P = 0.200) and complement C4A (1.83-fold increase; P = 0.007) in IGT subjects but not in healthy volunteers. Changes in C4A were also found in the serum samples of Zucker diabetic fatty (ZDF) rats after four weeks of PEB intake compared to basal levels (P = 0.042). In addition, an increased expression of the glucose transporter-2 (GLUT2) gene was observed in the jejunum (P = 0.003) of inositol-supplemented rats when compared to sucrose supplementation. This change was correlated with the observed change in C4A (P = 0.002). Our results suggest that the substitution of a common sugar source, such as sucrose, by a naturally-based, pinitol-enriched beverage induces changes in the insulin secretion pathway that could help to reduce blood glucose levels by protecting β-cells and by stimulating the insulin secretion pathway. This mechanism of action could have a relevant role in the prevention of insulin resistance and diabetes progression.

Dataset Information

Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy.

Publications

Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy.

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