Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches

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Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches. / Boer, Geke Aline; Holst, Jens Juul.

In: Biology, Vol. 9, No. 12, 473, 2020.

Research output: Contribution to journalReviewpeer-review

Harvard

Boer, GA & Holst, JJ 2020, 'Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches', Biology, vol. 9, no. 12, 473. https://doi.org/10.3390/biology9120473

APA

Boer, G. A., & Holst, J. J. (2020). Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches. Biology, 9(12), [473]. https://doi.org/10.3390/biology9120473

Vancouver

Boer GA, Holst JJ. Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches. Biology. 2020;9(12). 473. https://doi.org/10.3390/biology9120473

Author

Boer, Geke Aline ; Holst, Jens Juul. / Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches. In: Biology. 2020 ; Vol. 9, No. 12.

Bibtex

@article{b1dd6bae84cc4535915b27dea75964a4,
title = "Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches",
abstract = "Simple SummaryWhen we ingest a meal, our intestine secretes hormones that are released into the bloodstream. Amongst these hormones are the incretins hormones which stimulate the release of insulin from the pancreas which is essential for the regulation of in particular postprandial glucose concentrations. In patients with type 2 diabetes, the effect of the incretins is diminished. This is thought to contribute importantly to the pathophysiology of the disease. However, in pharmacological amounts, the incretins may still influence insulin secretion and metabolism. Much research has therefore been devoted to the development of incretin-based therapies for type 2 diabetes. These therapies include compounds that strongly resemble the incretins, hereby stimulating their effects as well as inhibitors of the enzymatic degradation of the hormones, thereby increasing the concentration of incretins in the blood. Both therapeutic approaches have been implemented successfully, but research is still ongoing aimed at the development of further optimized therapies.Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.",
keywords = "GIP, GLP-1, incretins, T2DM, GLUCAGON-LIKE PEPTIDE-1, DEPENDENT INSULINOTROPIC POLYPEPTIDE, GASTRIC-INHIBITORY POLYPEPTIDE, SENSING RECEPTOR CASR, BETA-CELL FUNCTION, GLP-1 RECEPTOR, FOOD-INTAKE, ENDOCRINE-CELLS, GIP RECEPTOR, BODY-WEIGHT",
author = "Boer, {Geke Aline} and Holst, {Jens Juul}",
year = "2020",
doi = "10.3390/biology9120473",
language = "English",
volume = "9",
journal = "Biology",
issn = "2079-7737",
publisher = "MDPI AG",
number = "12",

}

RIS

TY - JOUR

T1 - Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches

AU - Boer, Geke Aline

AU - Holst, Jens Juul

PY - 2020

Y1 - 2020

N2 - Simple SummaryWhen we ingest a meal, our intestine secretes hormones that are released into the bloodstream. Amongst these hormones are the incretins hormones which stimulate the release of insulin from the pancreas which is essential for the regulation of in particular postprandial glucose concentrations. In patients with type 2 diabetes, the effect of the incretins is diminished. This is thought to contribute importantly to the pathophysiology of the disease. However, in pharmacological amounts, the incretins may still influence insulin secretion and metabolism. Much research has therefore been devoted to the development of incretin-based therapies for type 2 diabetes. These therapies include compounds that strongly resemble the incretins, hereby stimulating their effects as well as inhibitors of the enzymatic degradation of the hormones, thereby increasing the concentration of incretins in the blood. Both therapeutic approaches have been implemented successfully, but research is still ongoing aimed at the development of further optimized therapies.Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

AB - Simple SummaryWhen we ingest a meal, our intestine secretes hormones that are released into the bloodstream. Amongst these hormones are the incretins hormones which stimulate the release of insulin from the pancreas which is essential for the regulation of in particular postprandial glucose concentrations. In patients with type 2 diabetes, the effect of the incretins is diminished. This is thought to contribute importantly to the pathophysiology of the disease. However, in pharmacological amounts, the incretins may still influence insulin secretion and metabolism. Much research has therefore been devoted to the development of incretin-based therapies for type 2 diabetes. These therapies include compounds that strongly resemble the incretins, hereby stimulating their effects as well as inhibitors of the enzymatic degradation of the hormones, thereby increasing the concentration of incretins in the blood. Both therapeutic approaches have been implemented successfully, but research is still ongoing aimed at the development of further optimized therapies.Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

KW - GIP

KW - GLP-1

KW - incretins

KW - T2DM

KW - GLUCAGON-LIKE PEPTIDE-1

KW - DEPENDENT INSULINOTROPIC POLYPEPTIDE

KW - GASTRIC-INHIBITORY POLYPEPTIDE

KW - SENSING RECEPTOR CASR

KW - BETA-CELL FUNCTION

KW - GLP-1 RECEPTOR

KW - FOOD-INTAKE

KW - ENDOCRINE-CELLS

KW - GIP RECEPTOR

KW - BODY-WEIGHT

U2 - 10.3390/biology9120473

DO - 10.3390/biology9120473

M3 - Review

C2 - 33339298

VL - 9

JO - Biology

JF - Biology

SN - 2079-7737

IS - 12

M1 - 473

ER -

ID: 255113225