open access

Vol 12, No 2 (2011): Practical Diabetology
Review articles (submitted)
Published online: 2011-08-05
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Fatty acid activated membrane receptor function and fat in the nutritional prevention of diabetes type 2

Danuta Rosołowska-Huszcz
Diabetologia Praktyczna 2011;12(2):42-51.

open access

Vol 12, No 2 (2011): Practical Diabetology
Review articles (submitted)
Published online: 2011-08-05

Abstract

The mechanisms of intracellular free fatty acid (FFA) effects on insulin secretion and signaling are known for many years, however, their effects exerted by extracellular route, via membrane receptors, have been recognized only recently. There are two main groups of membrane receptors activated by FFA: Toll like receptors (TLRs) engaged in nonspecific immunity, activated by bacterial and viral antigens and Gprotein coupled receptors (GPRs). Activation of TLR2 and 4 by saturated acids leads to activation of NFkB and induction of proinflammatory cytokines. Knockout of TLR2 or TLR4 protects from the effects of high fat diet — insulin resistance and beta-cell dysfunction. GPRs mediate insulinotropic effects of FFA exerted either directly on pancreatic beta cells (GPR- 40) or indirectly, in enteroendocrine cells, by stimulation of GLP-1 and GIP release (GPR-120). The effects of cholecystokinin, GLP-1 and GIP secretion through GPR-120 activation were shown for monounsaturated and polyunsaturated omega 3 fatty acids. In adipose tissue omega 3 fatty acids counteract the proinflammatory cytokine signaling and their synthesis. Short chain fatty acids utilize adipose GPR-43 for stimulation of leptin secretion and GPR-42 and 43 for stimulation of PYY and serotonin secretion by enteroendocrine cells. The intensive research of GPR ligands pharmacologically efficient in diabetes type 2 therapy are currently conducted. Comprehensive characterization of the effects of dietary fatty acids on GPR activation could enable the optimization of nutritional prevention and management of diabetes type 2.
(Diabet. Prakt. 2011; 12, 2: 42–51)

Abstract

The mechanisms of intracellular free fatty acid (FFA) effects on insulin secretion and signaling are known for many years, however, their effects exerted by extracellular route, via membrane receptors, have been recognized only recently. There are two main groups of membrane receptors activated by FFA: Toll like receptors (TLRs) engaged in nonspecific immunity, activated by bacterial and viral antigens and Gprotein coupled receptors (GPRs). Activation of TLR2 and 4 by saturated acids leads to activation of NFkB and induction of proinflammatory cytokines. Knockout of TLR2 or TLR4 protects from the effects of high fat diet — insulin resistance and beta-cell dysfunction. GPRs mediate insulinotropic effects of FFA exerted either directly on pancreatic beta cells (GPR- 40) or indirectly, in enteroendocrine cells, by stimulation of GLP-1 and GIP release (GPR-120). The effects of cholecystokinin, GLP-1 and GIP secretion through GPR-120 activation were shown for monounsaturated and polyunsaturated omega 3 fatty acids. In adipose tissue omega 3 fatty acids counteract the proinflammatory cytokine signaling and their synthesis. Short chain fatty acids utilize adipose GPR-43 for stimulation of leptin secretion and GPR-42 and 43 for stimulation of PYY and serotonin secretion by enteroendocrine cells. The intensive research of GPR ligands pharmacologically efficient in diabetes type 2 therapy are currently conducted. Comprehensive characterization of the effects of dietary fatty acids on GPR activation could enable the optimization of nutritional prevention and management of diabetes type 2.
(Diabet. Prakt. 2011; 12, 2: 42–51)
Get Citation

Keywords

GPR-40; GPR-120; Toll-like receptors; fatty acids; diabetes; dietary fat

About this article
Title

Fatty acid activated membrane receptor function and fat in the nutritional prevention of diabetes type 2

Journal

Clinical Diabetology

Issue

Vol 12, No 2 (2011): Practical Diabetology

Pages

42-51

Published online

2011-08-05

Bibliographic record

Diabetologia Praktyczna 2011;12(2):42-51.

Keywords

GPR-40
GPR-120
Toll-like receptors
fatty acids
diabetes
dietary fat

Authors

Danuta Rosołowska-Huszcz

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