Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats

Kumar, Peeyush T.; Antony, Sherin; Nandhu, Mohan S.; Sadanandan, Jayanarayanan; George, Naijil; Paulose, C S

doi:10.1016/j.jnutbio.2010.03.010

Cited by 37 publications

(28 citation statements)

References 40 publications

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“…STZ-induced diabetic rats have proved to be useful in trying to determine the underlying cause of liver complications during diabetes (9) . Similar to previous reports, in the present study, STZ-induced diabetes was characterised by hypoinsulinaemia, hyperglycaemia and decreased body weight (5,12) . Treatment with vitamin D 3 significantly improved hypoinsulinaemia and hyperglycaemia and prevented body-weight loss, which indicated amelioration in diabetic complications.…”

Section: Discussionsupporting

confidence: 92%

Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

George¹,

Kumar

Antony

et al. 2012

Br J Nutr

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Diabetes mellitus is a growing health problem worldwide and is associated with severe liver complications. The aim of the present study is to analyse the status of metabolic and free-radical-scavenging enzymes and second messengers in the liver of streptozotocin (STZ)-induced diabetic rats, and to determine the hepatoprotective role of vitamin D 3 . All studies were performed using the liver of adult male Wistar rats. Gene expression studies were carried out using real-time PCR with specific probes. Second messenger levels were determined using 3 H-labelled Biotrak assay kits, and glucose uptake assay with D-[ 14 C]glucose. The present results show that there was a decrease in hepatic glucose uptake, malate dehydrogenase activity, glycogen content, inositol triphosphate (IP 3 ) and cyclic GMP levels, and superoxide dismutase, glutathione peroxidase, phospholipase C, cyclic AMP-responsive element-binding protein, vitamin D receptor (VDR) and insulin receptor (INSR) gene expression in the diabetic rats when compared with the controls (all P,0·05), while cyclic AMP levels and GLUT2 expression were increased (P,0·05). Treatment of the diabetic rats with vitamin D 3 and insulin reversed the altered parameters to near control values. In conclusion, the data suggest a novel role of vitamin D 3 in restoring impaired liver metabolism in STZ-induced diabetic rats by regulating glucose uptake, storage and metabolism. We demonstrated that the restoring effect of vitamin D 3 is mediated through VDR modulation, thereby improving signal transduction and controlling free radicals in the liver of diabetic rats. These data suggest a potential role for vitamin D 3 in the treatment of diabetes-associated hepatic complications.Key words: Vitamin D: Diabetes: Liver: Oxidative stress: Metabolism: Insulin Diabetes-associated complications are major causes of morbidity and mortality. The liver plays a unique role in glucose homeostasis. Because of its anatomical location, it is ideally suited to control the systemic supply of absorbed nutrients, and it is one of only two organs that both consume and produce substantial amounts of glucose. The central role of the liver in the maintenance of blood glucose levels is assured by complex regulation by metabolic substrates, insulin and other hormones (1) . Diabetes-associated hyperglycaemia and hypoinsulinaemia lead to the impairment of hepatic glucose and lipid metabolism. Virtually, the entire spectrum of liver diseases is seen in patients with diabetes, including liver cirrhosis, a significant cause of death in diabetic patients, even more relevant than CVD (2) . Interest in the development of novel antidiabetic agents has been fuelled by the intense complications due to therapeutic treatment of diabetes and associated liver failure (2,3) . An increased prevalence of diabetes has been observed in vitamin D-deficient individuals (4) , and our previous study has shown that vitamin D 3 treatment restores blood glucose homeostasis in streptozotocin (STZ)-induced diabetic rats (5) . Bind...

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Section: Discussionsupporting

confidence: 92%

Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

George¹,

Kumar

Antony

et al. 2012

Br J Nutr

Self Cite

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“…Vitamin D 3 , as well as insulin, markedly recovers the altered gene expression of m 1 -and m 3 -MAChRs in the cerebral cortex and cerebellum of STZ rats and binding parameters of these receptors to near control (P.T. Kumar et al, 2011). Vitamin D 3 -induced improvement of the cholinergic system and glucose homeostasis in the diabetic brain is due to the influence of vitamin D 3 on activity of pancreatic m 3 -MAChR followed by enhanced synthesis and secretion of insulin and reduction of the neuronal disorders in DM (P.T.…”

Section: Acetylcholine Signalingmentioning

confidence: 90%

“…Vitamin D 3 -induced improvement of the cholinergic system and glucose homeostasis in the diabetic brain is due to the influence of vitamin D 3 on activity of pancreatic m 3 -MAChR followed by enhanced synthesis and secretion of insulin and reduction of the neuronal disorders in DM (P.T. Kumar et al, 2011). It was found, in addition, that vitamin D 3 restores the disrupted expression of IR in the cerebral cortex of diabetic rats.…”

Section: Acetylcholine Signalingmentioning

confidence: 92%

“…It was found, in addition, that vitamin D 3 restores the disrupted expression of IR in the cerebral cortex of diabetic rats. Curcumin possesses powerful anti-diabetic properties and has the ability to modulate MAChRs thereby ameliorating the impaired cognitive functions in DM (Peeyush Kumar et al, 2011). Ionotropic nicotine acetylcholine receptors are also involved in the pathogenesis of neurodegenerative processes in DM.…”

Section: Acetylcholine Signalingmentioning

confidence: 99%

“…In the cortex of STZ rats the expression of α7-nicotinic receptors was markedly increased. The receptors significantly influenced the activity within the cortex circuitry, and DM-associated deregulation of this activity could contribute to disorders involving the cerebral cortex (Peeyush Kumar et al, 2011). Alongside with the increase in α7-nicotinic receptors expression, in the cerebral cortex of diabetic rats were revealed the increased acetylcholine esterase and the decreased choline acetyl transferase mRNA levels, which indicates fast acetylcholine degradation and a subsequent down stimulation of acetylcholine receptors causing undesirable effects on cognitive functions.…”

Section: Acetylcholine Signalingmentioning

confidence: 99%

See 2 more Smart Citations

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Шпаков¹,

Chistyakova²,

Derkach³

et al. 2011

Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring

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Effect of vitamin D₃on behavioural and biochemical parameters in diabetes type 1‐induced rats

Calgaroto

Thomé

Costa

et al. 2014

Cell Biochemistry & Function

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Diabetes is associated with long-term complications in the brain and reduced cognitive ability. Vitamin D3 (VD3 ) appears to be involved in the amelioration of hyperglycaemia in streptozotocin (STZ)-induced diabetic rats. Our aim was to analyse the potential of VD3 in avoiding brain damage through evaluation of acetylcholinesterase (AChE), Na(+) K(+) -adenosine triphosphatase (ATPase) and delta aminolevulinate dehydratase (δ-ALA-D) activities and thiobarbituric acid reactive substance (TBARS) levels from cerebral cortex, as well as memory in STZ-induced diabetic rats. Animals were divided into eight groups (n = 5): control/saline, control/metformin (Metf), control/VD3 , control/Metf + VD3 , diabetic/saline, diabetic/Metf, diabetic/VD3 and diabetic/Metf + VD3 . Thirty days after treatment, animals were submitted to contextual fear-conditioning and open-field behavioural tests, after which they were sacrificed and the cerebral cortex was dissected. Our results demonstrate a significant memory deficit, an increase in AChE activity and TBARS levels and a decrease in δ-ALA-D and Na(+) K(+) -ATPase activities in diabetic rats when compared with the controls. Treatment of diabetic rats with Metf and VD3 prevented the increase in AChE activity when compared with the diabetic/saline group. In treated diabetic rats, the decrease in Na(+) K(+) -ATPase was reverted when compared with non-treated rats, but the increase in δ-ALA-D activity was not. VD3 prevented diabetes-induced TBARS level and improved memory. Our results show that VD3 can avoid cognitive deficit through prevention of changes in important enzymes such as Na(+) K(+) -ATPase and AChE in cerebral cortex in type 1 diabetic rats.

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Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats

Cited by 37 publications

References 40 publications

Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Effect of vitamin D₃on behavioural and biochemical parameters in diabetes type 1‐induced rats

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Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats

Cited by 37 publications

References 40 publications

Effect of vitamin D3in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

Effect of vitamin D3in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

Effect of vitamin D3on behavioural and biochemical parameters in diabetes type 1‐induced rats

Contact Info

Product

Resources

About

Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

Effect of vitamin D₃in reducing metabolic and oxidative stress in the liver of streptozotocin-induced diabetic rats

Effect of vitamin D₃on behavioural and biochemical parameters in diabetes type 1‐induced rats