Effects of Reg3 Delta Bioactive Peptide on Blood Glucose Levels and Pancreatic Gene Expression in an Alloxan-Induced Mouse Model of Diabetes

Siddique, Tehmina; Awan, Fazli Rabbi

doi:10.1016/j.jcjd.2015.09.096

Cited by 10 publications

(7 citation statements)

References 36 publications

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“…From the results, it was obvious that alloxan monohydrate significantly (P≤0.01) decreased the mRNA expression level of PDX-1, INS-1 and INS-2 genes. The mechanism involved might be the ROS production by alloxan in pancreatic beta cells, leads towards reduced expression level of PDX-1, which in turn is responsible for the suppression of other genes involved in insulin signaling cascade, such as insulin 1 (INS-1) and insulin 2 (INS-2) (Siddique and Rabbi, 2016). Results of current study have shown that mRNA expression of PDX-1, INS-1 and INS-2 genes was reversed by the polyherbal formulation extract treatment.…”

Section: Discussionmentioning

confidence: 99%

Polyherbal Formulation Prevents Hyperglycemia by Modulating the Biochemical Parameters and Upregulating the Insulin Signaling Cascade in Alloxan Induced Hyperglycemic Rats

Majeed¹

2018

PVJ

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Diabetes mellitus is a metabolic disorder having serious consequences on health and is becoming the 3 rd most fatal disease worldwide. The current study was designed to prepare and explore the antihyperglycemic potential of a polyherbal formulation comprising aqueous extracts of Momordica charantia, Syzygium cumini, Acacia nilotica, Elettaria cardamomum, Cicer arietinum L, Foeniculum vulgare and Gymnema sylvestre. Hyperglycemia was induced by alloxan monohydrate (150 mg/kg). After induction of diabetes, polyherbal formulation was administered in graded doses 200, 400 and 600mg/kg to treated groups I, II and III respectively. Polyherbal formulation was found to be rich in phytoconstituents on phytochemical analysis. Antihyperglycemic potential of polyherbal formulation was determined through biochemical and gene expression analysis. Results of the study revealed that polyherbal formulation significantly reversed the alloxan monohydrate induced hyperglycemia in rat models by improving the biochemical parameters in dose dependent manner. Highest dose of polyherbal formulation (600 mg/kg) significantly reduced the serum glucose (142.60±3.12 mg/dl), glycosylated hemoglobin (6.62±0.27%) and increased the serum insulin (16.87±1.53 U/L) levels in comparison to diabetic control group having serum glucose (375.20±8.98 mg/dl), glycosylated hemoglobin (13.92±0.70%) and insulin (6.26±1.13 U/L) levels respectively. Moreover, polyherbal formulation enhanced the performance of pancreatic β cells by upregulating the expression of PDX-1, INS-1 and INS-2 genes (insulin signaling cascade). Conclusively, the results of current study indicated the potent hypoglycemic properties of polyherbal formulation.

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Section: Discussionmentioning

confidence: 99%

Polyherbal Formulation Prevents Hyperglycemia by Modulating the Biochemical Parameters and Upregulating the Insulin Signaling Cascade in Alloxan Induced Hyperglycemic Rats

Majeed¹

2018

PVJ

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“…REG gene expression levels correlate with insulin secretory function (Madrid et al 2013) and treatment using INGAP, one of the subtypes of REG protein, enhances neonatal islet insulin secretion (Barbosa et al 2006, Madrid et al 2009). More importantly, REG protein expression is upregulated in diabetic human islets (Marselli et al 2010, Planas et al 2010, with animal models supporting their role as a compensatory factor during islet stress (Siddique & Awan 2016, Xia et al 2016. In regard to the downstream signaling pathway, ex vivo (keratinocytes) (Barbosa et al 2008, Lai et al 2012, Wu et al 2016 and in vivo (Xia et al 2016) studies have indicated that REG3G/REG3A protein binds to EXTL3, which subsequently activates AKT and/or STAT3 downstream signaling.…”

Section: Discussionmentioning

confidence: 99%

High glucose alters fetal rat islet transcriptome and induces progeny islet dysfunction

Casasnovas

Rao

et al. 2019

Journal of Endocrinology

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Journal of Endocrinology240:2 309-323 J Casasnovas, Y Jo et al. Fetal hyperglycemia induces islet hypofunction AbstractOffspring of diabetic mothers are susceptible to developing type 2 diabetes due to pancreatic islet dysfunction. However, the initiating molecular pathways leading to offspring pancreatic islet dysfunction are unknown. We hypothesized that maternal hyperglycemia alters offspring pancreatic islet transcriptome and negatively impacts offspring islet function. We employed an infusion model capable of inducing localized hyperglycemia in fetal rats residing in the left uterine horn, thus avoiding other factors involved in programming offspring pancreatic islet health. While maintaining euglycemia in maternal dams and right uterine horn control fetuses, hyperglycemic fetuses in the left uterine horn had higher serum insulin and pancreatic beta cell area. Upon completing infusion from GD20 to 22, RNA sequencing was performed on GD22 islets to identify the hyperglycemia-induced altered gene expression. Ingenuity pathway analysis of the altered transcriptome found that diabetes mellitus and inflammation/cell death pathways were enriched. Interestingly, the downregulated genes modulate more diverse biological processes, which includes responses to stimuli and developmental processes. Next, we performed ex and in vivo studies to evaluate islet cell viability and insulin secretory function in weanling and adult offspring. Pancreatic islets of weanlings exposed to late gestation hyperglycemia had decreased cell viability in basal state and glucose-induced insulin secretion. Lastly, adult offspring exposed to in utero hyperglycemia also exhibited glucose intolerance and insulin secretory dysfunction. Together, our results demonstrate that late gestational hyperglycemia alters the fetal pancreatic islet transcriptome and increases offspring susceptibility to developing pancreatic islet dysfunction.

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“…Results have shown that alloxan monohydrate significantly (P≤0.01) down regulated the Ins-1, Pdx-1 and IGF-1 mRNA expressions. The IGF-1 is a growth factor and has insulin-like effects on cell metabolism (Siddique and Awan, 2016). Pancreatic and duodenal homeobox factor-1 (Pdx-1) is expressed in the pancreas and duodenum and plays crucial role in pancreatic β-cells differentiation/regeneration (Kubo et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Polyherbal Formulation Ameliorates Diabetes Mellitus in Alloxan-Induced Diabetic Rats: Involvement of Pancreatic Genes Expression

Iftikhar¹

2018

PVJ

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Effects of Reg3 Delta Bioactive Peptide on Blood Glucose Levels and Pancreatic Gene Expression in an Alloxan-Induced Mouse Model of Diabetes

Cited by 10 publications

References 36 publications

Polyherbal Formulation Prevents Hyperglycemia by Modulating the Biochemical Parameters and Upregulating the Insulin Signaling Cascade in Alloxan Induced Hyperglycemic Rats

Polyherbal Formulation Prevents Hyperglycemia by Modulating the Biochemical Parameters and Upregulating the Insulin Signaling Cascade in Alloxan Induced Hyperglycemic Rats

High glucose alters fetal rat islet transcriptome and induces progeny islet dysfunction

Polyherbal Formulation Ameliorates Diabetes Mellitus in Alloxan-Induced Diabetic Rats: Involvement of Pancreatic Genes Expression

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