Journal
WORLD JOURNAL OF DIABETES
Volume 6, Issue 15, Pages 1285-1295Publisher
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.4239/wjd.v6.i15.1285
Keywords
Diabetes; Obesity; Incretin; Prediabetes; Gut hormones
Categories
Funding
- Diabetes United Kingdom
- European Foundation for the Study of Diabetes
- Invest Northern Ireland
- Irish Endocrine Society
- SAAD Trading and Contracting Company
- Department of Education and Learning Northern Ireland
- Diabetes Research Wellness Foundation
- University of Ulster
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The applicability of stable gut hormones for the treatment of obesity-related diabetes is now undisputable. This is based predominantly on prominent and sustained glucose-lowering actions, plus evidence that these peptides can augment insulin secretion and pancreatic islet function over time. This review highlights the therapeutic potential of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), oxyntomodulin (OXM) and cholecystokinin (CCK) for obesity-related diabetes. Stable GLP-1 mimetics have already been successfully adopted into the diabetic clinic, whereas GIP, CCK and OXM molecules offer promise as potential new classes of antidiabetic drugs. Moreover, recent studies have shown improved therapeutic effects following simultaneous modulation of multiple receptor signalling pathways by combination therapy or use of dual/triple agonist peptides. However, timing and composition of injections may be important to permit interludes of beta-cell rest. The review also addresses the possible perils of incretin based drugs for treatment of prediabetes. Finally, the unanticipated utility of stable gut peptides as effective treatments for complications of diabetes, bone disorders, cognitive impairment and cardiovascular dysfunction is considered.
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