The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival.

Currently available antidiabetic treatments fail to halt, and may even exacerbate, pancreatic ß-cell exhaustion, a key feature of type 2 diabetes pathogenesis; thus, strategies to prevent, or reverse, ß-cell failure should be actively sought. The serine threonine kinase Akt has a key role in the regulation of ß-cell homeostasis; among Akt modulators, a central role is played by pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) family. Here, taking advantage of an in vitro model of chronic exposure to high glucose, we demonstrated that PHLPPs, particularly the second family member called PHLPP2, are implicated in the ability of pancreatic ß cells to deal with glucose toxicity. We observed that INS-1 rat pancreatic ß cell line maintained for 12-15 passages at high (30 mM) glucose concentrations (INS-1 HG) showed increased expression of PHLPP2 and PHLPP1 both at mRNA and protein level as compared to INS-1 maintained for the same number of passages in the presence of normal glucose levels (INS-1 NG). These changes were paralleled by decreased phosphorylation of Akt and by increased expression of apoptotic and autophagic markers. To investigate if PHLPPs had a casual role in the alteration of INS-1 homeostasis observed upon chronic exposure to high glucose concentrations, we took advantage of shRNA technology to specifically knock-down PHLPPs. We obtained proof-of-concept evidence that modulating PHLPPs expression may help to restore a healthy ß cell mass, as the reduced expression of PHLPP2/1 was accompanied by a recovered balance between pro- and antiapoptotic factor levels. In conclusion, our data provide initial support for future studies aimed to identify pharmacological PHLPPs modulator to treat beta-cell survival impairment. They also contribute to shed some light on ß-cell dysfunction, a complex and unsatisfactorily characterized phenomenon that has a central causative role in the pathogenesis of type 2 diabetes.

Loss of Eyebrows and Eyelashes During Concomitant Treatment with Sitagliptin and Metformin.

The fixed dose combination of sitagliptin 50 mg and metformin 850 mg (Janumet ®), is indicated for the treatment of type 2 diabetes mellitus in addition to diet and exercise to improve glycemic control in patients treated with metformin alone. METHODS: We report a 69-year-old man with type 2 diabetes that developed sudden loss of eyebrows and eyelashes about 4 months after the beginning of Janumet®. Clinical and laboratory findings excluded the presence of systemic or skin diseases able to induce these manifestations, while the Naranjo probability scale documented a possible association between the drug and the adverse drug reaction.

Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile.

To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic eating habits.

[Glucagon-like peptide-1 analogues: effects on body weight and glycemia]. / Analoghi del glucagon-like peptide-1: effetti su glicemia e peso corporeo.

Glucagon-like peptide-1 (GLP-1) analogues-based therapies are a new option for type 2 diabetes treatment that hold the promise of overcoming the major limitations of traditional treatments, including the increased risk for hypoglycemia and weight gain. Herein, we review the data from clinical trials that have assessed the mechanism of action, the efficacy, and safety of exenatide and liraglutide, two analogues already available for therapy. The data of these trials showed that exenatide and liraglutide induced an improvement in glycemic control comparable with type 2 diabetes traditional treatments, as insulin, thiazolidinediones and sulfonylurea. GLP-1 analogues-based therapy was also associated with progressive weight reduction and a very low risk for hypoglycemia.