Nepton Soltani

The interplay between sympathetic nervous system activation and metabolic disorders, particularly type 2 diabetes mellitus (T2DM) and hypertension, has been increasingly recognized as a critical factor in cardiovascular morbidity and mortality. This review explores the potential mechanisms linking sympathetic overactivity to insulin resistance (IR) and T2DM, highlighting the role of renal denervation (RDN) as a promising therapeutic intervention. Sympathetic activation contributes to metabolic dysregulation by increasing plasma fatty acids, enhancing hepatic gluconeogenesis, and impairing pancreatic insulin release, while also inducing vasoconstriction and reducing glucose uptake in skeletal muscle. RDN, a catheter-based procedure targeting renal sympathetic nerves, has shown efficacy in managing resistant hypertension and improving glucose metabolism by reducing sympathetic drive, normalizing hepatic gluconeogenesis gene expression, and enhancing insulin sensitivity. Experimental and clinical studies suggest that RDN may mitigate IR, improve glycemic control, and reduce renal complications in diabetic models, independent of obesity or glucose tolerance status. However, the long-term effects on glycemic control and broader clinical applicability require further investigation.

Background and purpose: Diabetic nephropathy (DN) in the first and second generations of diabetic rats and improving kidney function by gamma aminobutyric acid (GABA) were investigated. Experimental approach: Male and female rats and their offspring were used. Diabetes was induced by a high-fat diet and a low dose of streptozotocin. Animals were divided into the diabetic positive control (D) group, the diabetic group receiving insulin (D + insulin), and the diabetic group receiving GABA (D + GABA). In addition, two groups of non-diabetic parents were assigned as negative control (NDC) groups. Each animal was monitored for 16 weeks, and offspring were fed with normal diet. The blood glucose level, urine volume, and water intake, as well as renal function, including the serum levels of blood urea nitrogen (BUN), creatinine (Cr), and glomerular filtration rate (GFR) were assessed. Also, the hyperinsulinemic-euglycemic clamp and gene expressions of Nox4 and Icaml in the kidneys were measured for all subjects. Findings/Results: GABA administration in parents and offspring decreased blood glucose level, insulin resistance, GFR, serum levels of BUN and Cr compared to the D groups. GABA reduced the urine Cr, BUN, and albumin loads in both parents and offspring in comparison to the D groups. GABA decreased Nox4 and Icaml gene expression in both parents and offspring. Conclusion and implications: GABA decreased the risk of DN, hyperglycemia, and insulin resistance in both diabetic parents and their offspring by improving kidney function, highlighting the potential therapeutic benefits of GABA in managing type 2 diabetes complications.

Metformin, a cornerstone treatment for type 2 diabetes, has recently emerged as a multifunctional therapeutic agent with applications extending far beyond glycemic control. This mini-review explores its promising roles within extracellular matrix (ECM)-based three-dimensional (3D) cell culture models, which closely mimic the in vivo cellular microenvironment. Through modulation of key pathways—including AMPK activation, inhibition of TGF-β signaling, suppression of aerobic glycolysis, and regulation of microRNAs—metformin exerts profound effects on ECM remodeling, fibrosis attenuation, and tumor progression. Furthermore, its integration into ECM-inspired drug delivery systems and regenerative scaffolds has shown great potential in applications such as diabetic wound healing, bone repair, and implant integration. Collectively, current findings highlight metformin as a versatile agent capable of modulating ECM biology in disease-specific 3D systems, paving the way for innovative therapeutic strategies in oncology, metabolic disorders, and tissue engineering.

Purpose. Gastric inflammation is common and usually severe in patients with type 2 diabetes mellitus (T2DM). Evidence suggests protease-activated receptors (PARs) are a link between inflammation and gastrointestinal dysfunction. Given that magnesium (Mg²⁺) deficiency is a highly prevalent condition in T2DM patients, we assessed the therapeutic role of Mg²⁺ on the factors involved in gastric inflammation in T2DM. Methods. A rat model of T2DM gastropathy was established using a long-term high-fat diet+a low dose of streptozocin. Twenty-four rats were divided into control, T2DM , T2DM+insulin (positive control), and T2DM+Mg²⁺ groups. At the end of 2-month therapies, changes in the expression of gastric trypsin-1, PAR1, PAR2, PAR3, PI3K/Akt, and COX-2 proteins were measured by western blot. Hematoxylin and eosin and Massons trichrome staining were used to detect gastric mucosal injury and fibrosis. Results. The expression of trypsin-1, PAR1, PAR2, PAR3, and COX-2 increased in diabetes, and Mg²⁺/insulin treatment strongly decreased their expression. The PI3K/p-Akt significantly decreased in T2DM, and treatment with Mg²⁺/insulin improved PI3K in T2DM rats. Staining of the gastric antrum tissue of the insulin/Mg²⁺-treated T2DM rats showed a significantly minimal mucosal and fibrotic injury compared with those of rats from the T2DM group. Conclusion. Mg²⁺ supplement, comparable to insulin, via decreasing PARs expression, mitigating COX-2 activity, and decreasing collagen deposition could exert a potent gastroprotective effect against inflammation, ulcer, and fibrotic development in T2DM patients.

The role of magnesium sulfate (MgSO₄) administration to prevent diabetic nephropathy (DN) by reducing insulin resistance (IR) and the relationship of this action with gender and the expression of NOX4 and ICAM1 genes in the parents and their offspring were studied. Males and females rat, and their pups were used. Type 2 diabetes induced by high-fat diet (HFD) administration and a low dose of streptozotocin. Animals were divided into the: non-treated diabetic (DC), the diabetic group received insulin (Ins), and the diabetic group received MgSO₄. Two groups of parents received just a normal diet (NDC). Following each set of parents for 16 weeks and their pups for 4 months, while eating normally. We assessed the amount of water consumed, urine volume, and blood glucose level. The levels of glucose, albumin, and creatinine in the urine were also measured, as well as the amounts of sodium, albumin, and creatinine in the serum. Calculations were made for glomerular filtration rate (GFR) and the excretion rates of Na and glucose fractions (FE Na and FE G, respectively). The hyperinsulinemic-euglycemic clamp was done. NOX4 and ICAM1 gene expressions in the kidney were also measured. MgSO₄ or insulin therapy decreased blood glucose, IR, and improved GFR, FE Na, and FE G in both parents and their offspring compared to D group. MgSO₄ improved NOX4 and ICAM1 gene expressions in the parents and their offspring compared to D group. Our results indicated that MgSO₄ could reduce blood glucose levels and insulin resistance, and it could improve kidney function.

Insulin resistance (IR) is a chronic pathological condition that is related to reduce the rates of glucose uptake, especially in the liver, muscle, and adipose tissue as target tissues. Metabolic syndrome and type 2 diabetes mellitus can occur following progression of the disease. The majority of prior research has applied that some cations such as magnesium (Mg²⁺) have important physiological role in insulin metabolism. Mg²⁺ is the fourth most abundant mineral in the human body that gets involved as a cofactor of various enzymes in several metabolic events, such as carbohydrate oxidation, and it has a fundamental role in glucose transporting mechanism of the cell membrane. This cation has numerous duties in the human body such as regulation of insulin secretion in pancreatic beta-cells and phosphorylation of the insulin receptors in target cells and also gets involved in other downstream signal kinases as intracellular cation. On this basis, intracellular Mg²⁺ balancing is vital for adequate carbohydrate metabolism. This paper summarizes the present knowledge about the therapeutic effects of Mg²⁺ in reducing IR in liver, muscle, and pancreases with different mechanisms. For this, the search was performed in Google Scholar, PubMed, Scopus, and Web of Science by insulin resistance, skeletal muscle, liver, pancreases, magnesium, Mg²⁺, and inflammation keywords.