In this review, we first summarize our traditional understanding of the physiology of GIP and GLP-1, and our current knowledge of the relationships between GIP and GLP-1 and obesity and diabetes.
These concepts are placed within the context of both normal physiology and the pathophysiology of disease, and then extended to discuss emerging strategies that incorporate glucagon agonism in the pharmacology of treating diabetes.
These studies highlight the clear, and persistent, metabolic advantages of sustained activation of GLP-1 receptors, alongside concurrent activation of related GIP and xenin cell signalling pathways, in diabetes.
While GIP shares common actions on the pancreatic beta cell with glucagon-like peptide-1 (GLP-1), unlike GLP-1, GIP presents a complex target for the development of diabetes and obesity therapies due to its extra-pancreatic effects on fat mass.
In several human studies, GLP-1 secretory responses to oral glucose load or a meal were decreased in subjects with obesity, glucose intolerance, or diabetes compared with those in healthy subjects.
Glucagon signaling increases hepatic glucose output, and hyperglucagonemia is partly responsible for the hyperglycemia in diabetes making glucagon an attractive target for therapeutic intervention.
The statistical correlation in glucagon levels between annual checkups and the sustained significant correlation between glucagon and blood urea nitrogen suggest a constant dysregulation of glucagon in association with altered amino acid metabolism in patients with type 1 diabetes.
Insulin and glucagon oppositely modulate blood glucose levels in health, but a combined decline in insulin secretion together with increased glucagon secretion contribute to hyperglycemia in diabetes.
Alpha-cell lineage tracing revealed that induction of diabetes was accompanied by increased (P < 0.01) transdifferentiation of glucagon positive alpha-cells to insulin positive beta-cells.
The present study aims to investigate the hypoglycemic mechanisms of DOP based on the glucagon-mediated signaling pathways and the liver glycogen structure, which catalyze hepatic glucose metabolism, and provide new knowledge about the antidiabetic mechanism of DOP and further evidence for its clinical use for diabetes.
Also, attention was diverted away from GIP by the successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, and a therapeutic strategy for GIP became uncertain when evidence emerged that both inhibition and enhancement of GIP action could prevent or reverse obese non-insulin dependent forms of diabetes in rodents.
GLP-1 therapy is effective concerning weight loss in overweight patients and is more often used in females and patients with shorter diabetes duration.
Individual without diabetes remission after gastric bypass have poorer β-cell response and lesser suppression of glucagon to an oral challenge; body weight and incretins differ minimally according to remission status.
The role of glucagon abnormality has recently been reported in type 2 diabetes; however, its role in gestational diabetes mellitus (GDM) is still unknown.
To determine the effect of exercise on plasma glucose, insulin, and glucagon concentrations in ITxs compared with control subjects (CONs) without diabetes.
Although agents based on glucagon-like peptide-1 (GLP-1) are now in routine use for diabetes and obesity, the limited efficacy of such drugs means that newer agents are required.
Diabetes is a chronic disease, and metabolic factors affecting brain metabolisms, such as serum glucose, insulin, and glucagon, are altered according to disease progression.
GLP-1, a peptide hormone secreted from the gut stimulating insulin and suppressing glucagon secretion was identified as a parent compound for novel treatments of diabetes, but was degraded (dipeptidyl peptidase-4) eliminated (mainly kidneys) too fast (half-life 1-2 min) to be useful as a therapeutic agent.
Diabetes increases the severity of impairment in PD, and GLP-1 improve it through its direct neuronal effect in addition to its indirect effect through producing hypoglycemia.
Our aim was to investigate the association between endogenous GLP-1 responses to oral glucose and peripheral and central haemodynamic measures in a population at risk of diabetes and CVD.