Administration of nicotinamide (NA) is followed by a pronounced hypoglycemic effect with a simultaneous decrease of glucose content in the lens, sciatic nerve and aorta at manifest streptozotocin-induced diabetes and also by a complete normalization of parameters of the intraperitoneal glucose-tolerance test in rats with a "diabetic" type of glucose tolerance. A 14-day NA treatment of patients with diabetes mellitus results in the improvement of the glycemic profile, a decrease of glucosuria and the blood serum level of protein-bound hexoses as well as positive shifts in the condition of the cardiovascular and nervous systems.
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Diabetes Metab J
January 2025
Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation.
View Article and Find Full Text PDFRen Fail
December 2025
Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Background: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) are antihyperglycemic agents that provide additional renal-protective effects in patients with DKD, independent of their glucose-lowering effects. However, the underlying mechanism remains unclear.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga-142 001 (Punjab), India. Electronic address:
The inhibition of enzyme DPP-4 is pivotal for targeting type 2 diabetes mellitus (DM). The study introduces two series of novel 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones derivatives (PB01-PB10) and 3,7-dihydro-1H-purine-2,6-diones compounds (PB11-PB16) were developed using linagliptin scaffold. Sixteen derivatives were synthesized and screened in vitro against DPP-4, revealing IC ranging from 15.
View Article and Find Full Text PDFNutrients
November 2024
Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan.
Background: With the global increase in metabolic disorders, identifying effective dietary strategies is crucial for enhancing health outcomes. While various health advantages of alkaline reduced water (ARW) have been documented, its specific impacts on glucose and lipid metabolism in both healthy and diabetic conditions are still not well understood.
Methods: This study investigates how ARW affects carbohydrate and lipid metabolism in male Wistar rats, which were induced to develop glucose metabolism disorders through subcutaneous injections of nicotinamide and streptozotocin (STZ).
Clin Pharmacol Ther
February 2025
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo City, Japan.
This study was designed to assess the quantitative performance of endogenous drug-drug interaction (DDI) biomarkers (N1-methylnicotinamide (1-NMN), N1-methyladenosine (mA), and creatinine) for the organic cation transporters, OCT2 and MATE1/2K in the kidney. Ten healthy volunteers received cimetidine (400 and 800 mg, single dose) or dolutegravir (50 mg, twice a day) together with metformin (500 mg). Cimetidine and dolutegravir were considered to act mainly as MATE1/2K and OCT2 inhibitors, respectively.
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