Propionate (0, 1, 2, 4, 8, 16, 32, and 64 mumol.kg BW-1 x min-1 for 30 min) was infused i.v. to investigate the physiological effects of propionate on insulin and glucagon responses in sheep. An i.v. propionate infusion (32 mumol.kg BW-1 x min-1 for 30 min) with adrenergic and cholinergic blockades was also conducted to clarify the role of autonomic innervation in the control of propionate-induced insulin and glucagon responses. In the experiment in which we studied responses to propionate infusion, the concentrations of plasma insulin and glucagon during propionate infusion increased (P < .05) from the preinfusion concentrations at infusion rates of > 4 and 8 mumol.kg BW-1 x min-1, respectively. The incremental response areas of plasma insulin and glucagon during propionate infusion increased (P < .05) at infusion rates of > 16 and 32 mumol.kg BW-1 x min-1, respectively. In the experiment studying the effects of adrenergic and cholinergic blockades on responses to propionate, the insulin incremental response area during propionate infusion was suppressed (P < .05) by atropine infusion but it was not influenced by phentolamine, propranolol, or hexamethonium infusions. The glucagon response area was suppressed (P < .05) by phentolamine infusion, but it was not influenced by propranolol, atropine, or hexamethonium infusions. It is concluded that in sheep 1) propionate may have a physiological role in stimulating insulin and glucagon responses, 2) the propionate-induced insulin response is partly due to the parasympathetic nervous system through activation of a muscarinic receptor, and 3) the propionate-induced glucagon response is stimulated by adrenergic alpha-receptors.
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http://dx.doi.org/10.2527/1993.71123414x | DOI Listing |
J Manag Care Spec Pharm
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Abbott Diabetes Care, Mississauga, Ontario, Canada.
Background: Both glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and continuous glucose monitoring (CGM) have been shown to improve glycated hemoglobin A1c (A1c) levels among patients with type 2 diabetes mellitus (T2DM). Recently, a US real-world study found statistically significant improvements in A1c levels among patients using GLP-1 RA and a CGM device, compared with a matched cohort receiving only GLP-1 RA.
Objectives: To assess the cost-effectiveness from a US payer perspective of initiating CGM (FreeStyle Libre Systems) in people living with T2DM using a GLP-1 RA therapy, compared with GLP-1 RA alone.
J Pharmacokinet Pharmacodyn
January 2025
Department of Clinical Pharmacy and Pharmacy Administration, West China school of Pharmacy, Sichuan University, Chengdu, 610064, China.
Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.
View Article and Find Full Text PDFDiabetologia
January 2025
Internal Medicine Department, Endocrine Division (SEMPR), Universidade Federal do Paraná, Curitiba, Brazil.
Aims/hypothesis: COMBINE 2 assessed the efficacy and safety of once-weekly IcoSema (a combination therapy of basal insulin icodec and semaglutide) vs once-weekly semaglutide (a glucagon-like peptide-1 analogue) 1.0 mg in individuals with type 2 diabetes inadequately managed with GLP-1 receptor agonist (GLP-1 RA) therapy, with or without additional oral glucose-lowering medications.
Methods: This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions.
J Clin Endocrinol Metab
January 2025
Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX.
Context: When clinically stable, patients with A-β+ Ketosis-Prone Diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.
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World J Diabetes
January 2025
Department of Gastroenterology, The First People's Hospital of Foshan, Foshan 528000, Guangdong Province, China.
In this article, we review the study by Jin , which examined the role of intestinal glucagon-like peptide-1 (GLP-1) in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus (T1DM). With the global rise of T1DM, there is an increased burden on society and healthcare systems. Due to insulin therapy and islet dysfunction, T1DM patients are highly vulnerable to severe hypoglycemia, a leading cause of mortality.
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