Insulin degradation. XXVIII. Immunocytochemical localization of glutathione-insulin transhydrogenase in the pancreas, kidney and liver of normal and streptozotocin-diabetic rats and of lean and obese (ob/ob) mice

Taylor, Catherine A.; Varandani, Partab T.

doi:10.1007/bf00257787

Cited by 9 publications

(4 citation statements)

References 30 publications

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“…A previous study [27] also reported few surviving disorganized islets with marked destruction of β cells in STZ-induced diabetic rats. A previous study [27] also reported few surviving disorganized islets with marked destruction of β cells in STZ-induced diabetic rats.…”

Section: Discussionmentioning

confidence: 68%

Effect of Nigella sativa on pancreatic β-cell damage in streptozotocin-induced diabetic rats

Omar

Atia

2012

The Egyptian Journal of Histology

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Nigella sativa (NS) is a spice plant belonging to the family Ranunculaceae [9]. It is a medical plant that contains black seeds and has been used as a natural remedy for a variety of illness. Nigella sativa L. contains greater than 30% of fixed oil and 0.40-0.45% (w/w) of volatile oil [10]. Volatile oil has been shown to have bronchodilator [10], antibacterial [11], diuretic, hypotensive [12], immunomodulatory [13], anti-inflammatory [14], antitumor [15], antidiabetic [16-18], and antiulcerogenic [19] effects. BackgroundDiabetes mellitus is a metabolic disease characterized by chronic hyperglycemia. Nigella sativa (NS) is a medical plant used as a natural remedy for a variety of illness. Aim of the studyThe aim of this study was to demonstrate the effect of NS on pancreatic β-cell damage and serum levels of glucose and insulin in streptozotocin (STZ)-induced diabetic rats and to correlate these effects with the immunohistochemical changes. Materials and methodsForty-five male albino rats were used in this study. The animals were divided into three groups: group I (control), group II (diabetic), and group III (diabetic with NS). Diabetes was induced in group II and III animals by a single intraperitoneal injection of STZ, 40mg/kg. Group III animals were given NS oil (0.2ml/kg/day) intraperitoneally for 4 weeks. Five rats from each group were sacrificed 2 days, and 2 and 4 weeks after STZ injection. Blood samples were collected for detection of serum glucose and insulin levels. Paraffin sections of the pancreas were prepared and stained with H&E stain and immunohistochemical stain using anti-insulin antibody. ResultsAfter STZ injection, the pancreatic islets appeared shrunken and showed degenerative changes and negative or weak positive insulin immunoreactivity. The serum level of insulin was decreased with elevation in the serum glucose concentration. NS injection improved the morphology of the islets, which nearly reverted to their normal size and structure with increased insulin immunoreactivity. NS also increased the lowered insulin and decreased the elevated glucose concentrations. Conclusion NS has a protective effect on pancreatic β-cell damage and improves serum levels of insulin and glucose in STZ-induced diabetic rats.

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Section: Discussionmentioning

confidence: 68%

Effect of Nigella sativa on pancreatic β-cell damage in streptozotocin-induced diabetic rats

Omar

Atia

2012

The Egyptian Journal of Histology

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“…When a supraphysiological concentration of insulin is used as substrate, GIT may be the most active of all insulin-degrading enzymes in the kidney, although GIT activity may be lower than normal in the kidneys of animals with chemically-induced diabetes. GIT, which is localized to the proximal tubule [61], reduces the disulphide bonds of insulin, producing separate, but intact, A and B chains, which can be degraded rapidly by the non-specific peptidases which are present in intracellular organelles [60], especially lysosomes. Together, GIT and lysosomal proteases could catalyze the initial, specific and later, non-specific steps, respectively, of insulin degradation by proximal tubular cells.…”

Section: Enzymatic Mechanisms Of Renal Insulin Degradationmentioning

confidence: 99%

The renal metabolism of insulin

1984

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The kidney plays a pivotal role in the clearance and degradation of circulating insulin and is also an important site of insulin action. The kidney clears insulin via two distinct routes. The first route entails glomerular filtration and subsequent luminal reabsorption of insulin by proximal tubular cells by means of endocytosis. The second involves diffusion of insulin from peritubular capillaries and subsequent binding of insulin to the contraluminal membranes of tubular cells, especially those lining the distal half of the nephron. Insulin delivered to the latter sites stimulates several important processes, including reabsorption of sodium, phosphate, and glucose. In contrast, insulin delivered to proximal tubular cells is degraded to oligopeptides and amino-acids by one of two poorly delineated enzymatic pathways. One pathway probably involves the sequential action of insulin protease and either GIT or non-specific proteases; the other probably involves the sequential action of GIT and lysosomal proteases. The products of insulin degradation are reabsorbed into the peritubular capillaries, apparently via simple diffusion. Impairment of the renal clearance of insulin prolongs the half-life of circulating insulin by a number of mechanisms and often results in a decrease in the insulin requirement of diabetic patients. Much needs to be learned about these metabolic events at the subcellular level and how they are affected by disease states. Owing to the heterogeneity of cell types within the kidney and to their anatomical and functional polarity, investigation of these areas will be challenging indeed.

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“…Insulin degradation is important in the regulation of insulin action; impairment in insulin clearance and degradation are present in various pathological conditions, including type-2 diabetes and obesity [29] . Diff erent amounts of insulin degrading activity were observed in various regions of tissues, like brain and peripheral tissues [30] . IDE can regulate 2 proteins, insulin and amyloid-β , each of which plays a central role in a common and devastating human disease.…”

Section: Discussion ▼mentioning

confidence: 99%

Inhibition of Insulin Degrading Enzyme by Racecadotril in the Brain of Wistar Rats

Lee¹,

Cheng

Chung

et al. 2011

Horm Metab Res

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Racecadotril is an enkephalinase inhibitor used to treat abdominal discomfort in the clinic. The blood-glucose lowering action of racecadotril has been observed in rats; however, the mechanisms remain obscure. 8-week-old Wistar rats were intravenously injected with racecadotril and the levels of insulin in the brain were measured. Additionally, brain homogenates were co-incubated with racecadotril or thiorphan to evaluate insulin degrading enzyme (IDE) activity. Otherwise, rats were pretreated by intracerebroventricular (i. c. v.) injection of insulin antibody or glibenclamide at a dose sufficient to inhibit K (ATP) channels prior to injection of racecadotril. Moreover, rats were vagotomized to evaluate the role of the cholinergic nerve. Racecadotril significantly decreased the plasma glucose in rats; this action of racecadotril was abolished by i. c. v. pretreatment with insulin antibody or glibenclamide. Also, i. c. v. injection of thiorphan, the active form of racecadotril, lowered blood glucose, but this effect disappeared in the presence of the insulin antibody. In rat brain homogenates, racecadotril and thiorphan inhibited IDE activity and increased the cerebral insulin level. The blood-glucose lowering action of racecadotril or thiorphan was diminished in vagotomized rats. Our results suggest that racecadotril lowers blood glucose mainly through inhibition of IDE activity and increases endogenous insulin in the brain. Subsequently, the increased insulin might activate insulin receptor, which opens the K (ATP) channel and induces peripheral insulin release through the vagal nerve. Thus, we provide the new finding that racecadotril has the ability to inhibit IDE in rat brain.

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Insulin degradation. XXVIII. Immunocytochemical localization of glutathione-insulin transhydrogenase in the pancreas, kidney and liver of normal and streptozotocin-diabetic rats and of lean and obese (ob/ob) mice

Cited by 9 publications

References 30 publications

Effect of Nigella sativa on pancreatic β-cell damage in streptozotocin-induced diabetic rats

Effect of Nigella sativa on pancreatic β-cell damage in streptozotocin-induced diabetic rats

The renal metabolism of insulin

Inhibition of Insulin Degrading Enzyme by Racecadotril in the Brain of Wistar Rats

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