Development of hypoglycemia, a slight decrease in concentration of glucagon in blood as well as increase in activity of malate-and glucose-6-phosphate dehydrogenases in liver cytosol were detected in rats injected subcutaneously with nicotinamide at a dose of 31.25 mg/kg 6 hrs before decapitation. Increase of the single dose up to 125 mg/kg caused hypoglycemia, distinct increase in concentration of insulin and glucagon in blood plasma simultaneously with a pronounced inhibition of the enzymatic activity in liver tissue. Effect of nicotinamide on carbohydrate metabolism appears to have a dissimilar character depending on the drug dose: its small doses accelerated utilization and oxidation of glucose but did not affect the secretion of insulin and glucagon.
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J Med Chem
January 2025
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
GPR119 has emerged as a promising target for treating type 2 diabetes and associated obesity, as its stimulation induces the secretion of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide in the intestinal tract as well as the glucose-dependent release of insulin in pancreatic β-cells. We describe the design and synthesis of novel GPR119 agonists containing a 1,4-disubstituted cyclohexene scaffold. Compound displayed nanomolar potency (EC = 3.
View Article and Find Full Text PDFMetabolites
January 2025
Department of Geriatric Medicine, Rotherham General Hospital, Moorgate Road, Rotherham S60 2UD, UK.
Frailty is an increasingly recognised complication of diabetes in older people and should be taken into consideration in management plans, including the use of the new therapies of sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon like peptide-1 receptor agonists (GLP-1RA). The frailty syndrome appears to span across a spectrum, from a sarcopenic obese phenotype at one end, characterised by obesity, insulin resistance, and prevalent cardiovascular risk factors, to an anorexic malnourished phenotype at the other end, characterised by significant weight loss, reduced insulin resistance, and less prevalent cardiovascular risk factors. Therefore, the use of the new therapies may not be suitable for every frail older individual with diabetes.
View Article and Find Full Text PDFCells
January 2025
Ralph H. Johnson Veterans Administration Medical Center, 109 Bee Street, Charleston, SC 29401, USA.
Rotenone, a naturally occurring compound derived from the roots of tropical plants, is used as a broad-spectrum insecticide, piscicide, and pesticide. It is a classical, high-affinity mitochondrial complex I inhibitor that causes not only oxidative stress, α-synuclein phosphorylation, DJ-1 (Parkinson's disease protein 7) modifications, and inhibition of the ubiquitin-proteasome system but it is also widely considered an environmental contributor to Parkinson's disease (PD). While prodromal symptoms, such as loss of smell, constipation, sleep disorder, anxiety/depression, and the loss of dopaminergic neurons in the substantia nigra of rotenone-treated animals, have been reported, alterations of metabolic hormones and hyperinsulinemia remain largely unknown and need to be investigated.
View Article and Find Full Text PDFInfect Dis Rep
January 2025
Royal Brompton Hospital, Part of GSTT NHS Foundation Trust, London SW3 6NP, UK.
Background: Glucagon-like peptide-1 (GLP-1) agonists are an existing treatment option for patients with insulin-resistant states, which elicit further pleiotropic effects related to immune cell recruitment and vascular inflammation. GLP-1 agonists downregulate the cluster of differentiation 147 (CD147) receptor, one of several receptors for the SARS-CoV-2 spike protein that mediate viral infection of host cells.
Methods: We conducted an open-label prospective safety and tolerability study including biomarker responses of the GLP-1 agonist Liraglutide, administered for 5 days as an add-on therapy to the standard of care within 48 h of presentation in a cohort of 13 patients hospitalized with COVID-19 pneumonia.
Diabet Med
January 2025
Steno Diabetes Center Copenhagen, Clinical Translational Research, Diabetes Technology Research, Herlev, Denmark.
Aims: This study was designed to compare the effectiveness of a single subcutaneous (s.c.) glucagon dose versus the same total dose split into a dose before and after and placebo (PBO) in preventing exercise-induced hypoglycaemia in adults with type 1 diabetes (T1D).
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