Direct Effects of D-Chiro-Inositol on Insulin Signaling and Glucagon Secretion of Pancreatic Alpha Cells

Filippello, Agnese; Scamporrino, Alessandra; Mauro, Stefania Di; Malaguarnera, Roberta; Pino, Antonino Di; Scicali, Roberto; Piro, Salvatore

doi:10.3390/biom10101404

Cited by 11 publications

(10 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 3-4 days of culture, organoids were exposed to increasing concentrations of glucose (from 17.5 mM to 25 mM and 35 mM) for extended periods (24, 48, and 72 h). After treatment, MTT (Sigma-Aldrich, Saint Louis, MO, USA) assay was performed as previously reported [41,42].…”

Section: Mtt Assaymentioning

confidence: 99%

High Glucose Exposure Impairs L-Cell Differentiation in Intestinal Organoids: Molecular Mechanisms and Clinical Implications

Filippello

Mauro

Scamporrino

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Intestinal organoids are used to analyze the differentiation of enteroendocrine cells (EECs) and to manipulate their density for treating type 2 diabetes. EEC differentiation is a continuous process tightly regulated in the gut by a complex regulatory network. However, the effect of chronic hyperglycemia, in the modulation of regulatory networks controlling identity and differentiation of EECs, has not been analyzed. This study aimed to investigate the effect of glucotoxicity on EEC differentiation in small intestinal organoid platforms. Mouse intestinal organoids were cultured in the presence/absence of high glucose concentrations (35 mM) for 48 h to mimic glucotoxicity. Chronic hyperglycemia impaired the expression of markers related to the differentiation of EEC progenitors (Ngn3) and L-cells (NeuroD1), and it also reduced the expression of Gcg and GLP-1 positive cell number. In addition, the expression of intestinal stem cell markers was reduced in organoids exposed to high glucose concentrations. Our data indicate that glucotoxicity impairs L-cell differentiation, which could be associated with decreased intestinal stem cell proliferative capacity. This study provides the identification of new targets involved in new molecular signaling mechanisms impaired by glucotoxicity that could be a useful tool for the treatment of type 2 diabetes.

show abstract

Section: Mtt Assaymentioning

confidence: 99%

High Glucose Exposure Impairs L-Cell Differentiation in Intestinal Organoids: Molecular Mechanisms and Clinical Implications

Filippello

Mauro

Scamporrino

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…When glucagon is inappropriately high or is inadequately produced in response to glucose levels there are metabolic imbalances that go beyond glycemic levels, given by, for instance, the delayed response to hypoglycemia or the excessive hepatic glucose release after glucagon stimulus. These aspects, as widely known, are often observed in diabetic patients and they go beyond simple hypoglycemia [ 124 ]. Severe hypoglycemia, for instance, is an index of glucagon disequilibrium and impairment of alpha pancreatic cells.…”

Section: Glucagon: Insulin Antidote or Main Driver Of Diabetes Homeostasis?mentioning

confidence: 99%

Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

et al. 2021

Self Cite

View full text Add to dashboard Cite

Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in itself, is a risk for patients and relatives. The possibility to have novel strategies and scientific knowledge concerning hypoglycemia could represent an enormous benefit. Novel available glucagon formulations, even now, allow clinicians to deal with hypoglycemia differently with respect to past years. Novel scientific evidence leads to advances concerning physiopathological mechanisms that regulated glycemic homeostasis. In this review, we will try to show some of the important aspects of this field.

show abstract

“…Protein was extracted from 80 mg of liver tissue with RIPA lysis buffer and Western blot was made as previously reported [ 21 ]. All the immunoblot signals were detected using the Odyssey Fc System Infrared Scanner (LI-COR Biosciences, Lincoln, NE, USA) and densitometric analyses were performed by using Odyssey software Image Studio Lite Ver 5.2.…”

Section: Methodsmentioning

confidence: 99%

Coffee Restores Expression of lncRNAs Involved in Steatosis and Fibrosis in a Mouse Model of NAFLD

Mauro

Salomone²,

Scamporrino

et al. 2021

Nutrients

Self Cite

View full text Add to dashboard Cite

Background and aim: Coffee intake exerts protective effects against non-alcoholic fatty liver disease (NAFLD), although without fully cleared mechanisms. In this study we aimed to assess whether coffee consumption may influence the expression of long non-coding RNAs (lncRNAs) in the liver. Methods: C57BL/6J mice were fed a 12-week standard diet (SD), high-fat diet (HFD) or HFD plus decaffeinated coffee solution (HFD + coffee). Expression of specific lncRNAs involved in NAFLD was analyzed by real-time PCR. For the most differentially expressed lncRNAs, the analysis was also extended to their mRNA targets. Results: Decaffeinated coffee intake reduced body weight gain, prevented NAFLD, lowered hyperglycemia and hypercholesterolemia. NAFLD was associated with lower hepatic expression of Gm16551, a lncRNA inhibiting de novo lipogenesis, and higher expression of H19, a lncRNA promoting fibrogenesis. Coffee intake restored Gm16551 to levels observed in lean mice and downregulated gene expression of its targets acetyl coenzyme A carboxylase 1 and stearoyl coenzyme A desaturase 1. Furthermore, coffee consumption markedly decreased hepatic expression of H19 and of its target gene collagen alpha-1(I) chain; consistently, in mice fed HFD + coffee liver expression of αSMA protein returned to levels of mice fed SD. Expression of lncRNA involved in circadian clock such as fatty liver-related lncRNA 1 (FLRL1) and fatty liver-related lncRNA 2 (FLRL2) were upregulated by HFD and were also modulated by coffee intake. Conclusion. Hepatoprotective effects of coffee may be depending on the modulation of lncRNAs involved in key pathways of NAFLD onset and progression.

show abstract

Direct Effects of D-Chiro-Inositol on Insulin Signaling and Glucagon Secretion of Pancreatic Alpha Cells

Cited by 11 publications

References 65 publications

High Glucose Exposure Impairs L-Cell Differentiation in Intestinal Organoids: Molecular Mechanisms and Clinical Implications

High Glucose Exposure Impairs L-Cell Differentiation in Intestinal Organoids: Molecular Mechanisms and Clinical Implications

Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

Coffee Restores Expression of lncRNAs Involved in Steatosis and Fibrosis in a Mouse Model of NAFLD

Contact Info

Product

Resources

About