Association between the membrane transporter proteins and type 2 diabetes mellitus

ABSTRACT

Introduction: The prevalence rate of diabetes is increasing day by day and the current scenario of the available agents for its treatment has given rise to stimulation in the search for new therapeutic targets and agents. Therefore the present review will examine the role of membrane composition in the pathophysiology of Type 2 Diabetes and the possible therapeutic approaches for this.

Areas covered: Glucose transporter proteins (GLUTs) are integral membrane proteins which are responsible for facilitated glucose transport over the plasma membrane into cells. Thus, this chapter is an attempt to interpret the co-relation between membrane transporter proteins and lipid molecules of cell membrane and their implications in type 2 diabetes mellitus. The relationship between the composition controlled flexibility of the membrane in the insertion of GLUTs into cell membrane as well as its fusion with the membrane is the focus of this chapter.

Expert opinion: There is increasing data on the central role of phospholipid composition toward T2DM. Plasma membrane lipid composition plays a key role in maintaining the machinery for insulin-independent GLUT insertion into the membrane as well as insulin-dependent GLUT4 containing vesicles. As a therapeutic option, the designing of new chemical entities should be aimed to decrease saturated fatty acids of lipid bilayer phospholipids to target type 2 diabetes mellitus.

KEYWORDS:

• Type 2 diabetes mellitus
• cell membranes
• glucose transporter proteins
• unsaturated fatty acids
• anionic lipids

Article Highlights

• Type 2 Diabetes Mellitus is currently one of the most severe global health problems with significantly high prevalence rate and is the root of several other metabolic consequences.

• Recent studies highlight the role of plasma membrane in the expression and action of glucose transporter proteins responsible for the cellular glucose transport.

• The present review examines the possible connection between membrane lipid composition and fluidity, and fusion and translocation of vesicles containing glucose transporters in the pathophysiology of Type 2 Diabetes.

• The increase in the ratio of polyunsaturated fatty acids to saturated fatty acids reduces the membrane flexibility followed by a reduction in glucose transporters and thereby, reducing their glucose transport activity.

• Therefore, potential therapeutic agents targeting either modulation of the plasma membrane composition or signaling proteins–membranes interactions could be valuable avenues for novel therapeutic applications.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.