Nuclear lamins and diabetes mellitus

Wei Xie,Brian Burke

doi:10.37175/stemedicine.v2i5.73

Abstract

In metazoans, a thin filamentous network referred to as the nuclear lamina plays an essential role in providing mechanical support to the nucleus. The major constituent of the nuclear lamina is type V intermediate filament proteins that are collectively referred to as lamins. A variety of diseases collectively termed laminopathies have been linked to mutations in genes encoding nuclear envelope proteins, in particular lamins, such as X-linked Emery Dreifus muscular dystrophy, dilated cardiomyopathy, Dunnigan type familial partial lipodystrophy and Hutchinson-Gilford progeria syndrome. Apart from laminopathies, genome-wide association studies have also been implicated nuclear lamins in the pathophysiology of type 2 diabetes mellitus, although little information in terms of the function of lamins in its pathogenesis. Our current review attempts to summarize risk factors of diabetes mellitus that could be attributable to lamin mutations and indirectly linked to lamin-associated factors identified in the last two decades.

Highlights

The nucleus and nuclear lamins Eukaryotic cells are defined by the presence of a nucleus enclosed by a pair of lipid bilayers, the outer nuclear membrane (ONM) and the inner nuclear membrane (INM), that together comprise the nuclear envelope (NE) [1]
Studies employing a Lmna deficient mouse strain, which develops a syndrome that bears a striking resemblance to human Emery Dreifus muscular dystrophy (EDMD), revealed that Lamin A and C can associate with Emerin and that these two lamins are required for Emerin localization to the INM, at least in fibroblasts and muscle cells
familial partial lipodystrophy (FPLD) patients typically present symptoms that include subcutaneous fat loss, glucose intolerance, hypertension and insulin resistance, along with other characteristic changes associated with metabolic syndrome that eventually lead to diabetes mellitus (DM) (Figure 2)

Summary

Introduction

The nucleus and nuclear lamins Eukaryotic cells are defined by the presence of a nucleus enclosed by a pair of lipid bilayers, the outer nuclear membrane (ONM) and the inner nuclear membrane (INM), that together comprise the nuclear envelope (NE) [1]. The two major A-type lamins, A and C, are encoded by the LMNA gene and are derived by alternative splicing of the same primary transcript. Lamins and associated diseases A variety of diseases have been linked to mutations in genes encoding NE proteins.

Results

Conclusion