Intron specific polymorphic site of vaspin gene along with vaspin circulatory levels can influence pathophysiology of type 2 diabetes

Rathwa, Nirali; Parmar, Nishant; Palit, Sayantani Pramanik; Patel, Roma; Ramachandran, A. V.; Begum, Rasheedunnisa

doi:10.1016/j.lfs.2020.117285

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…Our previous reports suggest interleukin 1β (IL1β) 22 , resistin 23 and TNFα 24 to play an important role in the development of obesity, islet dysfunction and decreased insulin secretion. On the contrary, adiponectin 2 , omentin-1 25 , melatonin 26 and vaspin 27 are known to enhance insulin sensitivity. The normal range of total adiponectin in healthy individuals is reported to be 2-20 µg/mL 28 .…”

Section: Discussionmentioning

confidence: 99%

A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes

Palit

Patel

Jadeja

et al. 2020

Sci Rep

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Adiponectin is a prime determinant of the status of insulin resistance. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (Snps) and metabolic diseases have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we investigated (1) the association between ADIPOQ Snps: −11377C/G, +10211T/G, +45T/G and +276G/T for the risk towards type 2 diabetes (T2D) and, (2) genotype-phenotype association of these SNPs with various biochemical parameters in two cohorts. Genomic DNA of diabetic patients and controls from Gujarat and, Jammu and Kashmir (J&K) were genotyped using PCR-RFLP, TaqMan assay and MassArray. transcript levels of ADIPOQ were assessed in visceral adipose tissue samples, and plasma adiponectin levels were estimated by qPCR and ELISA respectively. Results suggest: (i) reduced HMW adiponectin/ total adiponectin ratio in Gujarat patients and its association with +10211T/G and +276G/T, and reduced ADIPOQ transcript levels in T2D, (ii) association of the above SNPs with increased FBG, BMI, TG, TC in Gujarat patients and (iii) increased GGTG haplotype in obese patients of Gujarat population and, (iv) association of −11377C/G with T2D in J&K population. Reduced HMW adiponectin, in the backdrop of obesity and ADIPOQ genetic variants might alter metabolic profile posing risk towards T2D.Metabolic Syndrome (MS) is the new wave of diseases that has hit the human population in the last few decadesthe Metabolic Syndrome Era. It has become pandemic and with obesity and type 2 diabetes (T2D) clubbed under the MS umbrella, millions of people around the globe have come under its grip. Though obesity and T2D are ubiquitous, there exists a pattern of prevalence based on ethnicity. A recent report has identified demographic transitions, nutrition and lifestyle in the backdrop of genetic predisposition as the chief factors responsible for the rising trend of obesity associated amongst South Asians 1 . Over accumulation of visceral adipose tissue (AT) has been identified as one of the major driving factors towards T2D. Adipose tissue is an important regulator of metabolic homeostasis by virtue of the adipokines (pro-inflammatory and anti-inflammatory) that it secretes. In obese conditions, the fine-tuned balance between the pro-and anti-inflammatory adipokines gets altered leading to various metabolic disorders 2 . These bioactive peptides act locally and distally to calibrate and fine tune various metabolic pathways. Adiponectin is one such calibrator which is abundantly expressed in white adipose tissue 3 . It circulates in three polymorphic forms, low molecular weight (LMW), moderate molecular weight (MMW) and high molecular weight (HMW). Interestingly, the ratio of plasma HMW adiponectin to total adiponectin is more strongly correlated with plasma glucose levels than any of the forms alone 4 . Adiponectin gene (ADIPOQ/ APM1/GBP28) locus, 3q27, has been strongly associated with a variety of metabolic disorders like-impaired glucose tolerance, obesity, dys...

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Section: Discussionmentioning

confidence: 99%

A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes

Palit

Patel

Jadeja

et al. 2020

Sci Rep

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“…Many of these adipokines are crucial in maintaining the status of insulin sensitivity of peripheral tissues viz. adipose tissue and skeletal muscle (Pramanik et al, 2017, Patel et al, 2016Patel et al, 2018;Patel et al, 2019;Rathwa et al, 2019 a & b;Rathwa et al, 2020). In view of this, regulating hyperglycaemia by merely regulating the hepatic glucose out-put or enhancing glucose clearance seem superficial.…”

Section: Discussionmentioning

confidence: 99%

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

Patel

Parmar

et al. 2021

Preprint

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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 β-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-β, pAkt/Akt, and AdipoR1 were restored in the skeletal muscle and a significant increase in islet number as a result of β-cell regeneration and reduced β-cell death were also observed in the combination drug treated group. Thus, L-glutamine and pitavastatin in combination can induce β-cell regeneration and regulate glucose homeostasis to bring about amelioration of HFD+STZ induced T2D.

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“…After sacrificing the mice, peripheral tissues such as liver, AT and SK were dissected and stored in RNAlater™ Stabilization Solution (Thermo Fisher Scientific, USA). Total RNA was extracted by the Trizol method as described previously [8]. The expression of targeted genes and GAPDH transcripts were monitored by LightCycler®480 Real-time PCR (Roche Diagnostics GmbH, Germany) using gene-specific primers (Eurofins, India) [Table S1].…”

Section: Gene Expression Profilingmentioning

confidence: 99%

“…Dysfunctional adipocytes and β -cells are involved in advancing obesity-induced type 2 diabetes (T2D) [1]. Several aspects regulate the progression of T2D, such as genetic predisposition [2][3][4][5][6][7][8][9], excess calorie intake [1,10] and sedentary lifestyle [10], all of which cause persistent hyperglycemia and eventual β -cell apoptosis. Even though there have been many recent management therapies for T2D, none can withstand the worsening condition of β -cell loss.…”

Section: Introductionmentioning

confidence: 99%

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

Rathwa

Parmar

et al. 2021

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Aim: Dysfunctional adipocytes and β-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 γ-aminobutyric acid (GABA), a neurotransmitter secreted by β-cells, exerts regenerative effects. Methods: High-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 β-cell regeneration and apoptosis was analysed by IHC. Results: CR+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-1α 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. Conclusion: Our results suggest that CR in combination with GABA ameliorates T2D in HFD+STZ treated mice, by GABA induced β-cell regeneration and CR mediated insulin sensitivity.

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Intron specific polymorphic site of vaspin gene along with vaspin circulatory levels can influence pathophysiology of type 2 diabetes

Cited by 6 publications

References 38 publications

A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes

A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes

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

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

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