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SHR Neuro Krebs Kardio Lipid

Vinod, M; Patankar, JV; Sachdev, V; Frank, S; Graier, WF; Kratky, D; Kostner, GM.
MiR-206 is expressed in pancreatic islets and regulates glucokinase activity.
Am J Physiol Endocrinol Metab. 2016; 311(1): E175-E185. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Frank Saša
Graier Wolfgang
Kostner Gerhard
Kratky Dagmar
Patankar Jay Vasant
Sachdev Vinay
Vinod Manjula
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Number of Figures: 6
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Abstract:
Glucose homeostasis is a complex indispensable process, and its dysregulation causes hyperglycemia and type 2 diabetes mellitus. Glucokinase (GK) takes a central role in these pathways and is thus rate limiting for glucose-stimulated insulin secretion (GSIS) from pancreatic islets. Several reports have described the transcriptional regulation of Gck mRNA, whereas its posttranscriptional mechanisms of regulation, especially those involving microRNAs (miR), are poorly understood. In this study, we investigated the role of miR-206 as a posttranscriptional regulator of Gck In addition, we examined the effects of miR-206 on glucose tolerance, GSIS, and gene expression in control and germ line miR-206 knockout (KO) mice fed either with chow or high-fat diet (HFD). MiR-206 was found in Gck-expressing tissues and was differentially altered in response to HFD feeding. Pancreatic islets showed the most profound induction in the expression of miR-206 in response to HFD. Chow- and HFD-fed miR-206KO mice have improved glucose tolerance and GSIS but unaltered insulin sensitivity. In silico analysis of Gck mRNA revealed a conserved 8-mer miR-206 binding site. Hence, the predicted regulation of Gck by miR-206 was confirmed in reporter and GK activity assays. Concomitant with increased GK activity, miR-206KO mice had elevated liver glycogen content and plasma lactate concentrations. Our findings revealed a novel mechanism of posttranscriptional regulation of Gck by miR-206 and underline the crucial role of pancreatic islet miR-206 in the regulation of whole body glucose homeostasis in a murine model that mimics the metabolic syndrome. Copyright © 2016 the American Physiological Society.

Find related publications in this database (Keywords)
miR-206
glucose sensing
insulin sensitivity
glucose tolerance
pancreatic islets
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