Biology subjects

Rathwa, N.

Publications and source records attributed to Rathwa, N..

3 recordsLinked to original sources

bioRxiv2025

Melatonin and GABA monotherapies are as efficacious as combination therapy in managing T1D and T2D: In-vivo studies on experimental diabetic models

BackgroundLoss of functional {beta}-cell mass is a critical factor in the ontogenesis of type 1 (T1D) and type 2 diabetes (T2D) marked by chronic hyperglycemia. Melatonin (M) and {gamma}-aminobutyric acid (GABA/G) have immunoregulatory properties and have shown potential to increase {beta}-cell mass in experimental diabetic models. Thus, we aimed to investigate the therapeutic potential of melatonin combined with GABA on {beta}-cell regeneration in streptozotocin (STZ)-induced T1D and on a high-fat diet (HFD)-induced T2D mouse models. MethodsThe BALB/c mice were injected with 50 mg/kg body weight STZ on five consecutive days to induce T1D and were subjected to six weeks of monotherapy with melatonin or GABA and combination therapy (M+G). HFD was fed to C57BL/6J mice for 30 weeks to induce insulin resistance and T2D, followed by six weeks of mono or combination therapy exposure. ResultsOur studies on monotherapies and combination therapy reduced fasting blood glucose levels, increased plasma insulin levels and glucose tolerance, and promoted {beta}-cell proliferation and transdifferentiation, with a simultaneous decrease in {beta}-cell apoptosis in T1D mice. It also improved metabolic parameters and glycolipid metabolism in the liver and adipose tissue, respectively, and increased mitochondrial function in the skeletal muscle. Moreover, it restored peripheral insulin sensitivity and {beta}-cell mass in T2D mice. ConclusionOur studies suggest that monotherapies are as effective as combination therapy since melatonin and GABA sub-additively ameliorates T1D and T2D manifestations.

biochemistry↗

bioRxiv2021

Calorie Restriction in combination with GABA: improved glycaemic control in type 2 diabetes mouse model

AimDysfunctional adipocytes and {beta}-cells are crucial in the advancement of obesity-induced type 2 diabetes (T2D). Calorie restriction (CR) improves insulin sensitivity and fasting blood glucose (FBG) levels, while {gamma}-aminobutyric acid (GABA), a neurotransmitter secreted by {beta}-cells, exerts regenerative effects. MethodsHigh-fat diet (HFD) and streptozotocin (STZ) induced T2D mouse model was used to assess the effect of CR and GABA combination therapy. The mice were fed with CR diet (30% reduction of HFD) and treated with GABA (2.5 mg/kg i.p) daily for 5 weeks. Assessment of FBG, body weight (BW), insulin sensitivity, glucose tolerance, and estimation of plasma insulin and lipid profile were carried out by standard methods. The mRNA expression of target genes [liver (glucoregulatory enzymes), adipose tissue (lipid metabolism markers) and skeletal muscle (mitochondrial biogenesis markers)] was assessed by SYBR Green-qPCR. Oxygen consumption rate for mitochondrial complex I, II and III was measured in skeletal muscle using Oxytherm Clark-type oxygen electrode. The effect of monotherapies and combination treatment on pancreatic {beta}-cell regeneration and apoptosis was analysed by IHC. ResultsCR+GABA group showed significant reduction in FBG levels, improved lipid profile and whole-body insulin responsiveness as indicated by increased insulin levels, insulin sensitivity and glucose tolerance compared to the monotherapies. The transcript expression profile of glucoregulatory enzymes in the liver showed significant reduction in G6Pase, PEPCK, Glycogen Phosphorylase and increased GCK expression in CR+GABA group as compared to the monotherapies The ACC and ATG expression was up-regulated in adipose tissue; and significant increase in SIRT-1, PGC-1 and TFAM expression with up-regulated mitochondrial complex I and III activities was observed in CR+GABA group as compared to the monotherapies. Percentage of BrdU/Insulin and PDX1/Ngn3/Insulin co-positive cells was significantly higher in CR+GABA treated group than the monotherapy and HFD+STZ groups. Finally, there was a significant reduction in TUNEL/Insulin co-positive cells suggesting reduced apoptosis in CR+GABA treated group. ConclusionOur results suggest that CR in combination with GABA ameliorates T2D in HFD+STZ treated mice, by GABA induced {beta}-cell regeneration and CR mediated insulin sensitivity.

physiology↗

bioRxiv2021

Repurposing statin and L-glutamine: replenishing β-cells in hyperlipidemic T2D mouse model

While cases of obesity-induced type 2 diabetes (T2D) are on the upswing, current therapies help only manage the symptoms. Of late, L-glutamine has been implicated in the amelioration of T2D by virtue of its glucagon like peptide-1 (GLP-1) secretagogue property. Alongside, there are mixed reports on adiponectin (insulin sensitizer) potentiating property of statins. We aimed to investigate the effect of pitavastatin (P) and L-glutamine (LG) combination on glycemic control and pancreatic {beta}-cell regeneration in a high-fat diet (HFD)+Streptozotocin (STZ) induced T2D mouse model. C57BL6/J mice treated with HFD+STZ were randomly assigned into four groups: Diabetic control, L-glutamine, Pitavastatin and P+LG. Control group was fed with the chow diet. Significant amelioration in insulin resistance along with plasma glucose, lipid profile, adiponectin levels, and mitochondrial complexes I, II, III activities were observed in P+LG group as compared to HFD+STZ treated group. Phosphoenolpyruvate carboxykinase, glucose 6-phophatase, glycogen phosphorylase, and GLUT2 transcript levels were reduced with increased glycogen synthase transcript levels in liver. Further, the protein levels of Insulin receptor 1-{beta}, pAkt/Akt, and AdipoR1 were restored in the skeletal muscle and a significant increase in islet number as a result of {beta}-cell regeneration and reduced {beta}-cell death were also observed in the combination drug treated group. Thus, L-glutamine and pitavastatin in combination can induce {beta}-cell regeneration and regulate glucose homeostasis to bring about amelioration of HFD+STZ induced T2D.

biochemistry↗