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The Expanded Endocannabinoid System/Endocannabinoidome as a Potential Target for Treating Diabetes Mellitus

Abstract

Purpose of Review

The endocannabinoid (eCB) system, i.e. the receptors that respond to the psychoactive component of cannabis, their endogenous ligands and the ligand metabolic enzymes, is part of a larger family of lipid signals termed the endocannabinoidome (eCBome). We summarize recent discoveries of the roles that the eCBome plays within peripheral tissues in diabetes, and how it is being targeted, in an effort to develop novel therapeutics for the treatment of this increasingly prevalent disease.

Recent Findings

As with the eCB system, many eCBome members regulate several physiological processes, including energy intake and storage, glucose and lipid metabolism and pancreatic health, which contribute to the development of type 2 diabetes (T2D). Preclinical studies increasingly support the notion that targeting the eCBome may beneficially affect T2D.

Summary

The eCBome is implicated in T2D at several levels and in a variety of tissues, making this complex lipid signaling system a potential source of many potential therapeutics for the treatments for T2D.

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Fig. 1

Abbreviations

AcArGs:

1-acyl-sn-2-arachidonoyl-glycerols

2-AG:

2-arachidonoyl-glycerol

2-MAG:

2-mono-acyl-glycerol

2-OG:

2-oleoylglycerol

2-PG:

2-palmitoylglycerol

abn-CBD:

abnormal cannabidiol

AA:

arachidonic acid

AEA:

arachidonoylethanolamide

CB1/2:

cannabinoid receptor type-1/2

THC:

D9-tetrahydrocannabinol

THCV:

D9-Tetrahydrocannabivarin

DAGL:

diacylglycerol lipase

DHEA:

docohexanoylethanolamide

eCB:

endocannabinoid

eCBome:

endocannabinoidome

FAAH:

fatty acid amide hydrolase

GPR119:

G protein-coupled Receptor 119

GPR55:

G protein-coupled Receptor 55

GIP:

glucose-dependent insulinotropic polypeptide

LEA:

linoleoylethanolamide

MAGL:

monoacylglycerol lipase

NAE:

N-acylethanolamine

NAPE-PLD:

N-acyl-phosphatidylethanolamine-specific phospholipase D-like

NArPEs:

N-arachidonoyl-phosphatidylethanolamines

NAFLD:

nonalcoholic fatty liver disease

OEA:

oleoylethanolamide

PEA:

palmitoylethanolamide

SEA:

stearoylethanolamide

TRPV1:

transient receptor potential cation channel subfamily V member 1

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Correspondence to Cristoforo Silvestri.

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Alain Veilleux declares no conflict of interest.

Vincenzo Di Marzo reports grants from GW Pharmaceuticals.

Cristoforo Silvestri reports he was a previous employee of GW Pharmaceuticals.

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Veilleux, A., Di Marzo, V. & Silvestri, C. The Expanded Endocannabinoid System/Endocannabinoidome as a Potential Target for Treating Diabetes Mellitus. Curr Diab Rep 19, 117 (2019). https://doi.org/10.1007/s11892-019-1248-9

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Keywords

  • Endocannabinoidome
  • Bioactive lipids
  • Peripheral tissues
  • Glucose
  • Insulin