Duodenal-Jejunal Bypass Restores Insulin Action and Βeta-Cell Function in Hypothalamic-Obese Rats

Bonfleur, Maria Lúcia; Ribeiro, Rosane Aparecida; Pavanello, Audrei; Soster, Raul; Lubaczeuski, Camila; Araujo, Allan Cezar Faria; Boschero, Antônio Carlos; Balbo, Sandra Lucinei

doi:10.1007/s11695-014-1427-3

Cited by 7 publications

(8 citation statements)

References 58 publications

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“…Regarding the lipidic metabolism in MSG rats, although there are some discrepancies among our data on unmodified peripheral TG concentrations, it must be mentioned that other researchers found enhanced basal TG levels where they have taken those samples at 8 or more hours after food was withdrawn (fasting condition) [ 40 , 41 ]. When analyzing peripheral TG levels in response to LPS in MSG rats, it has been shown that MSG rats, over development, display reduced lipolytic and enhanced lipogenic activities [ 42 ], thus indicating that after the allostatic load (LPS injection) the balance of activities strongly support for the enhanced MSG AUC of this lipid [ 43 , 44 ].…”

Section: Discussioncontrasting

confidence: 59%

Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats

Castrogiovanni

Ongaro

Zuburía

et al. 2015

International Scholarly Research Notices

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Rats neonatally treated with monosodium L-glutamate (MSG) are deeply dysfunctional in adulthood. We explored the effect of an oral low dose of metformin treatment in male MSG rats on adipoinsular axis and visceral adipose tissue (VAT) dysfunctions, in both basal (nonfasting) and endotoxemia conditions. MSG rats, treated or not treated with metformin (30 days prior to experimentation), and control litter-mates (CTR) were studied at 90 days of age. Peripheral concentrations of glucose, lipids, and hormones were determined in basal and post-lipopolysaccharide (LPS) treatment conditions. Food intake and body weight (BW) were recorded and VAT mass and leptin mRNA levels were evaluated. Data indicated that MSG rats were lighter and displayed hypercorticosteronemia, hypophagia, adipoinsular axis hyperactivity, and enhanced VAT mass associated with an increased leptin gene expression. Interestingly, metformin-treated MSG rats corrected BW catch-up and counteracted VAT (mass and leptin mRNA level) and adipoinsular axis (basal and post-LPS) dysfunctions. Thus metformin treatment in MSG rats is able to correct several VAT and metabolic-endocrine dysfunctions. Our study suggests that a low-dose metformintherapy is effective to correct, at least in part, adipoinsular axis dysfunction in hypertrophic obese phenotypes, such as that of the human Cushing syndrome.

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Section: Discussioncontrasting

confidence: 59%

Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats

Castrogiovanni

Ongaro

Zuburía

et al. 2015

International Scholarly Research Notices

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“…This assumption is further supported by the fact that fasting serum insulin levels did not differ between the groups ( Table 2 ). Moreover, measurements of Akt phosphorylation at basal non-stimulated conditions have been reported by others [ 65 , 66 , 67 , 68 ]. Collectively, our data demonstrates that EA exerts anti-diabetic effects, consistent with previous findings [ 21 , 60 , 69 , 70 ].…”

Section: Discussionmentioning

confidence: 82%

Ellagic Acid Alleviates Hepatic Oxidative Stress and Insulin Resistance in Diabetic Female Rats

et al. 2018

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Non-alcoholic fatty liver disease (NAFLD) affects more than 70% of patients with type 2 diabetes mellitus (T2DM) and has become one of the most common metabolic liver diseases worldwide. To date, treatments specifically targeting NAFLD do not exist. Oxidative stress and insulin resistance have been implicated in the pathogenesis of NAFLD in diabetes. Accordingly, the goal of this present study was to determine whether Ellagic acid (EA), a natural antioxidant polyphenol found in berries and nuts, mitigates hepatic oxidative stress and insulin resistance in T2DM rats, and thus alleviates NAFLD. Using adult female Goto Kakizaki (GK) rats, a non-obese and spontaneous model of T2DM, we found that EA treatment significantly lowered fasting blood glucose and reduced insulin resistance, as shown by a 21.8% reduction in the homeostasis model assessment index of insulin resistance (HOMA-IR), while triglyceride and total cholesterol levels remained unchanged. Increased hepatic lipid accumulation and oxidative stress present in diabetic GK rats was markedly reduced with EA treatment. This effect was associated with a downregulation of the NADPH oxidase subunit, p47-phox, and overexpression of NF-E2-related factor-2 (NRF2). Moreover, EA was able to decrease the hepatic expression of hypoxia-inducible factor (HIF-α), a transcription factor linked to hypoxia and hepatic steatosis. We further showed that EA treatment activated an insulin signaling pathway in the liver, as evidenced by increased levels of phosphorylated Akt (Ser 473). In conclusion, our results demonstrate that EA diminishes blood glucose levels and potently suppress NAFLD in diabetic rats via mechanisms that involve reductions in p47-phox and HIF-α, upregulation of NRF2 and enhancement of the Akt signaling pathway in the liver. Together, these results reveal that EA improves hepatic insulin sensitivity and lipid metabolism as a result of its antioxidant effects. This implies an anti-diabetic effect of EA with beneficial effects for the treatment of hepatic complications in T2DM.

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“…DJB surgery, independent of changes in body adiposity, seems to be a good strategy to improve glucose homeostasis in pre-diabetic and diabetic experimental rodents and patients (13,18). However, the effects of DJB intervention upon the morphofunction of the endocrine pancreas are largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…This effect may contribute to the normalization of islet and β-cell percentage per pancreas section in the HyO pancreas, contributing to normalize the β-cell secretory capacity. In addition, the improvement in hyperinsulinemia and insulin sensitivity in HyO DJB rats (18), may also be involved in such process.…”

Section: Discussionmentioning

confidence: 99%

“…MSG-obese rats presented morbid obesity, NAFLD, glucose intolerance, insulin resistance, hyperinsulinemia, hyperleptinemia, and pancreatic islet hyperfunction (15–17). DJB surgery in MSG-treated rats does not decrease adiposity and hepatic steatosis, but ameliorates body glucose control and hepatic insulin action (18). Thus, we aimed to better understand the mechanism of action by which DJB surgery regulates hepatic lipid metabolism and pancreatic islet morphophysiology in HyO rats.…”

Section: Introductionmentioning

confidence: 99%

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Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats

Cantelli

Soares

Ribeiro

et al. 2017

Braz J Med Biol Res

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Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in β-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, β-cell hypersecretion, a higher percentage of islets and β-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.

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Duodenal-Jejunal Bypass Restores Insulin Action and Βeta-Cell Function in Hypothalamic-Obese Rats

Abstract: DJB ameliorated glucose homeostasis, restored hepatic insulin action, and normalized islet function in HyO rats, indicating that this surgery may be useful for the treatment of hypothalamic obesity.

Cited by 7 publications

References 58 publications

Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats

Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats

Ellagic Acid Alleviates Hepatic Oxidative Stress and Insulin Resistance in Diabetic Female Rats

Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats

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