title: Induction of oxidative stress, suppression of glucose-induced insulin release, ATP production, glucokinase activity, and histomorphometric changes in pancreatic islets of hypothyroid rat.
abstract: Thyroid hormones have important role in metabolism and impairment of glucose metabolism and insulin secretion has been shown in hypothyroid rats but the exact mechanisms for this defect are poorly understood. The aim of this study was to investigate the effect of hypothyroidism on oxidative stress parameters, insulin secretory pathway and histomorphometric changes of pancreas. In the isolated islets of the control and methimazole -treated hypothyroid insulin secretion and content, ATP production, Glucokinase, and hexokinase specific activity and kATP and L-type channels sensitivity were assayed. In order to determine oxidative stress parameters, antioxidant enzymes and lipid peroxidation were measured in pancreatic homogenates. Histomorphometric changes and histochemistry of the islet in both groups were compared. Results showed that plasma glucose and insulin concentration and their area under the curve during IPGTT in hypothyroid group were respectively higher and lower than the controls. In the hypothyroid islets, glucose stimulated insulin secretion, ATP production, hexokinase and glucokinase activities were decreased. Hypothyroid induced a significant increased lipid peroxidation, and decreased the antioxidant enzyme activity. Compared with the control group, insulin antibody positivity, the total volume of the pancreas, islets, and the total number as well as the mean volume of the beta cells were also significantly decreased in the hypothyroid group. These findings indicate that oxidative stress produced under hypothyroidism could have a role in progression of pancreatic β-cell dysfunction, reduced beta cell mass and decreased glucokinase activity, impairing glucose tolerance and insulin secretion.
authors: Department of Physiology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Sepideh
authors: S
authors: Safayee
authors: Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Physiology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: karbalai@sums.ac.ir.
authors: Narges
authors: N
authors: Karbalaei
authors: Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Ali
authors: A
authors: Noorafshan
authors: Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Elham
authors: E
authors: Nadimi
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006593:Hexokinase / Q000378:metabolism; D007037:Hypothyroidism / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D054086:KATP Channels / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D000975:Antioxidants; D020746:Calcium Channels, L-Type; D007328:Insulin; D054086:KATP Channels; D013963:Thyroid Hormones; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose; D003981:Diazoxide; D005905:Glyburide
keywords: Beta cell mass; Histomorphometry; Hypothyroidism; Insulin secretion; Oxidative stress