A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion.

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB).

Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes?

Recent approval of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, tirzepatide, for the management of type 2 diabetes mellitus (T2DM) has reinvigorated interest in exploitation of GIP receptor (GIPR) pathways as a means of metabolic disease management. However, debate has long surrounded the use of the GIPR as a therapeutic target and whether agonism or antagonism is of most benefit in management of obesity/diabetes. This controversy appears to be partly resolved by the success of tirzepatide.

Chronic exposure to incretin metabolites GLP-1(9-36) and GIP(3-42) affect islet morphology and beta cell health in high fat fed mice.

The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to their major circulating metabolites GLP-1(9-36) and GIP(3-42). This study investigates the possible effects of these metabolites, and the equivalent exendin molecule Ex(9-39), on pancreatic islet morphology and constituent alpha and beta cells in high-fat diet (HFD) fed mice. Male Swiss TO-mice (6-8 weeks-old) were maintained on a HFD or normal diet (ND) for 4 months and then received twice-daily subcutaneous injections of GLP-1(9-36), GIP(3-42), Ex(9-39) (25 nmol/kg bw) or saline vehicle (0.

Sustained metabolic benefits of ΔTRTX-Ac1, a tarantula venom-derived peptide, when administered together with exenatide in high-fat fed mice.

Aim: The aim of the present study was to assess the long-term therapeutic efficacy of a recently discovered 28 amino acid peptide, Δ-theraphotoxin-Ac1 (Δ-TRTX-Ac1), originally isolated from venom of the Aphonopelma chalcodes tarantula. Δ-TRTX-Ac has previously been shown to improve pancreatic beta-cell function and suppress appetite.

Materials And Methods: Δ-TRTX-Ac1 was administered twice daily in high-fat fed (HFF) mice with streptozotocin (STZ)-induced insulin deficiency, namely HFF/STZ mice, for 28 days both alone and in combination with the venom-derived glucagon-like peptide-1 (GLP-1) mimetic, exenatide.

Peptides originally derived from Chilobrachys jingzhao tarantula venom possess beneficial effects on pancreatic beta cell health and function.

Clinical approval of the glucagon-like peptide-1 (GLP-1) mimetic exenatide for the treatment of type 2 diabetes highlights the therapeutic effectiveness of venom-derived peptides. In the present study, we examined and characterised the glucose-lowering potential of synthetic Jingzhaotoxin IX and Jingzhaotoxin XI peptides, which were originally isolated from the venom of the Chinese earth tarantula Chilobrachys jingzhao. Following confirmation of lack of beta-cell toxicity of synthetic peptides, assessment of enzymatic stability and effects on in vitro beta-cell function were studied, alongside putative mechanisms.