The hexosamine biosynthetic pathway can mediate myocardial apoptosis in a rat model of diet-induced insulin resistance

Rajamani, Uthra; Joseph, Danzil; Roux, Saartjie; Essop, M. Faadiel

doi:10.1111/j.1748-1716.2011.02275.x

Cited by 24 publications

(23 citation statements)

References 33 publications

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“…Treatment with hesperetin and glibenclamide in diabetic rats showed significant reduction in hexoses due to improved glycemic control. The level of hexosamine, increased significantly in the plasma and tissues of diabetic rats which may be due to insulin deficiency, this leads to depressed utilization of glucose by insulin-dependent pathway, thereby enhancing the formation of hexose and hexosamine [12].…”

Section: Discussionmentioning

confidence: 99%

The Role of Hesperetin in the Management of Diabetes Mellitus and Its Complications

Revathy¹

2017

JCTR

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Diabetes mellitus is a chronic metabolic disease which is a serious global problem. Many antidiabetic therapies focus on improving insulin sensitivity, increasing insulin production, and/or decreasing the level of blood glucose. Hesperetin is a flavanoid commonly found in many herbal medicines and food. Hesperetin seem to demonstrate adequate properties. Animal studies were carried out for 45days and at the end of 45 th day blood samples were collected and various biochemical parameters were measured using autoanalyser. They can inhibit enzymes involved in glucose metabolism, prevent the development of insulin resistance and normalize plasma glucose and insulin levels. This synthetic drug apart from producing a hypoglycemic effect has also been found to manifest hypolipidemic and anti-obesity activity. Hesperetin is also promising agents in the prevention of diabetic complications. They have strong antioxidant activity and inhibit the formation of advanced glycation end products, implicated in the pathogenesis of diabetic nephropathy, embryopathy, and neuropathy or impaired wound healing. Until now very few clinical studies have been concerned with the application of Hesperetin in treating diabetes. Our experimental findings with respect to the mechanism of action of synthetic compound in Streptozotocin induced diabetic rats suggest that it enhances insulin secretion by the islets of langerhans and enhances glucose utilization. However, due to their great therapeutic potential, these compounds deserve special attention.

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Section: Discussionmentioning

confidence: 99%

The Role of Hesperetin in the Management of Diabetes Mellitus and Its Complications

Revathy¹

2017

JCTR

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“…Total O-GlcNAc expression was evaluated by SDS-PAGE as described previously (51,52). Briefly, frozen heart and liver tissues were homogenized with modified ice-cold RIPA buffer, and the supernatant was centrifuged twice at 13,000 g for 10 min at 4°C and then stored at Ϫ80°C until further use.…”

Section: Methodsmentioning

confidence: 99%

“…Nonoxidative glucose pathways include the formation of advanced glycation end products (AGEs), the hexosamine biosynthetic pathway (HBP), and (in part) the pentose phosphate shunt. Previous studies have indicated greater oxidative stress and increased flux through these pathways in obesity (48,51,52); however, the interaction among these pathways is not well understood, nor is it clear how they are impacted by G6PD deficiency. A decrease in oxidant stress in G6PD-deficient myocardium could decrease flux through other nonoxidative pathways of glucose metabolism, resulting in an overall beneficial effect on cardiac structure and function (16,21).…”

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confidence: 99%

Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets

Hecker

Mapanga

Kimar

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzymopathy that affects cellular redox status and may lower flux into nonoxidative pathways of glucose metabolism. Oxidative stress may worsen systemic glucose tolerance and cardiometabolic syndrome. We hypothesized that G6PD deficiency exacerbates diet-induced systemic metabolic dysfunction by increasing oxidative stress but in myocardium prevents diet-induced oxidative stress and pathology. WT and G6PD-deficient (G6PDX) mice received a standard high-starch diet, a high-fat/high-sucrose diet to induce obesity (DIO), or a high-fructose diet. After 31 wk, DIO increased adipose and body mass compared with the high-starch diet but to a greater extent in G6PDX than WT mice (24 and 20% lower, respectively). Serum free fatty acids were increased by 77% and triglycerides by 90% in G6PDX mice, but not in WT mice, by DIO and high-fructose intake. G6PD deficiency did not affect glucose tolerance or the increased insulin levels seen in WT mice. There was no diet-induced hypertension or cardiac dysfunction in either mouse strain. However, G6PD deficiency increased aconitase activity by 42% and blunted markers of nonoxidative glucose pathway activation in myocardium, including the hexosamine biosynthetic pathway activation and advanced glycation end product formation. These results reveal a complex interplay between diet-induced metabolic effects and G6PD deficiency, where G6PD deficiency decreases weight gain and hyperinsulinemia with DIO, but elevates serum free fatty acids, without affecting glucose tolerance. On the other hand, it modestly suppressed indexes of glucose flux into nonoxidative pathways in myocardium, suggesting potential protective effects.

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“…These variations mediate the clock-dependent regulation of OGlcNAc transferase and O-GlcNAcase levels and nutrient metabolism and uptake. This would involve the coordinated regulation of the hexosamine biosynthetic pathway and play an important role in not only insulin resistance [103] but also myocardial apoptosis in the diet-induced insulin resistant rat [104] which in turn conversely depends critically on an adequate dark-phase. Any stress could increase flux through the HBP, leading to detrimental effects on the level of the cardiomyocyte [29,104].…”

Section: Active Phase Inactive Phasementioning

confidence: 99%

“…This would involve the coordinated regulation of the hexosamine biosynthetic pathway and play an important role in not only insulin resistance [103] but also myocardial apoptosis in the diet-induced insulin resistant rat [104] which in turn conversely depends critically on an adequate dark-phase. Any stress could increase flux through the HBP, leading to detrimental effects on the level of the cardiomyocyte [29,104]. As the O-GlcNAcylation of proteins show clear circadian patterns and is high during the active phase and low during the inactive phase, it is thus proposed to have major consequences in the rat model of insulin resistance [93].…”

Section: Active Phase Inactive Phasementioning

confidence: 99%

Importance of Dietary Fatty Acid Profile and Experimental Conditions in the Obese Insulin-Resistant Rodent Model of Metabolic Syndrome

Krygsman¹

2012

Glucose Tolerance

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The hexosamine biosynthetic pathway can mediate myocardial apoptosis in a rat model of diet-induced insulin resistance

Abstract: The main finding of this study is that increased apoptosis in hyperglycaemic/insulin-resistant hearts can also be mediated through HBP-induced BAD O-GlcNAcylation and greater formation of BAD-Bcl-2 dimers (pro-apoptotic).

Cited by 24 publications

References 33 publications

The Role of Hesperetin in the Management of Diabetes Mellitus and Its Complications

The Role of Hesperetin in the Management of Diabetes Mellitus and Its Complications

Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets

Importance of Dietary Fatty Acid Profile and Experimental Conditions in the Obese Insulin-Resistant Rodent Model of Metabolic Syndrome

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