Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice

Kanda, Yukiko; Hashiramoto, Mitsuru; Shimoda, Masashi; Hamamoto, Sumiko; Tawaramoto, Kazuhito; Kimura, Tomohiko; Hirukawa, Hidenori; Nakashima, Koji; Kaku, Kohei

doi:10.1016/j.jnutbio.2014.10.007

Cited by 31 publications

(29 citation statements)

References 35 publications

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“…Restricting the caloric intake also has beneficial effects on body weight and metabolic control 17–19. Based on these observations, we therefore examined the effects of combined treadmill training and CR on the diabetic state in the leptin-resistant mouse.…”

Section: Resultsmentioning

confidence: 99%

“…Moderate CR decreases visceral fat and blood pressure and improves the lipid profile, glucose uptake, and insulin sensitivity, and hearts from CR rodents show an improved ischemic tolerance 13–16. Furthermore, CR preserves pancreatic mass and function by suppressing apoptosis in the db/db mouse,17 attenuates the development of hepatic steatosis in the db/db mice,18 and decreases adiposity in the genetically hyperphagic OLEFT model of type 2 diabetes 19. Taken together, it is clear that the benefits of ET and CR share a common favorable outcome on cardiovascular and metabolic health 20…”

Section: Introductionmentioning

confidence: 99%

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The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Jankowski

Gutkowska

2017

DMSO

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BackgroundRegular exercise training (ET) and caloric restriction (CR) are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT)–natriuretic peptide (NP) system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity.MethodsFive-week-old male db/db mice were assigned to the following groups: sedentary, ET, and ET + CR. Nonobese heterozygote littermates served as controls. ET was performed on a treadmill at moderate intensity, and CR was induced by reducing food intake by 30% of that consumed by sedentary db/db mice for a period of 8 weeks.ResultsAfter 8 weeks, only ET + CR, but not ET, slightly improved body weight compared to sedentary db/db mice. Regardless of the treatment, db/db mice remained hyperglycemic. Hearts from db/db mice demonstrated reduced expression of genes linked to the cardiac OT–NP system. In fact, compared to control mice, mRNA expression of GATA binding protein 4 (GATA4), OT receptor, OT, brain NP, NP receptor type C, and endothelial nitric oxide synthase (eNOS) was decreased in hearts from sedentary db/db mice. Both ET alone and ET + CR increased the mRNA expression of GATA4 compared to sedentary db/db mice. Only ET combined with CR produced increased eNOS mRNA and protein expression.ConclusionOur data indicate that enhancement of eNOS by combined ET and CR may improve coronary endothelial vasodilator dysfunction in type 2 diabetes but did not prevent the downregulation of cardiac expression in the OT–NP system, possibly resulting from the sustained hyperglycemia and obesity in diabetic mice.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Jankowski

Gutkowska

2017

DMSO

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“…Furthermore, both classical ER stress due to misfolded protein and other environmental cues, such as feeding (lipid and glucose fluctuations) can trigger UPR (Kanda et al. 2015). Bimodal ATF6 target gene expression in the liver, which reflects bimodal feeding patterns (i.e.…”

Section: Discussionmentioning

confidence: 99%

Hepatic rhythmicity of endoplasmic reticulum stress is disrupted in perinatal and adult mice models of high-fat diet-induced obesity

Soeda

Cordero

et al. 2016

International Journal of Food Sciences and Nutrition

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We investigated the regulation of hepatic ER stress in healthy liver and adult or perinatally programmed diet-induced non-alcoholic fatty liver disease (NAFLD). Female mice were fed either obesogenic or control diet before mating, during pregnancy and lactation. Post-weaning, offspring from each maternal group were divided into either obesogenic or control diet. At six months, offspring were sacrificed at 4-h intervals over 24 h. Offspring fed obesogenic diets developed NAFLD phenotype, and the combination of maternal and offspring obesogenic diets exacerbated this phenotype. UPR signalling pathways (IREα, PERK, ATF6) and their downstream regulators showed different basal rhythmicity, which was modified in offspring exposed to obesogenic diet and maternal programming. The double obesogenic hit increased liver apoptosis measured by TUNEL staining, active caspase-3 and phospho-JNK and GRP78 promoter methylation levels. This study demonstrates that hepatic UPR is rhythmically activated. The combination of maternal obesity (MO) and obesogenic diets in offspring triggered altered UPR rhythmicity, DNA methylation and cellular apoptosis.

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“…Although the attenuation of oxidative stress in pancreatic islet cells by SGLT2 inhibitors is a possible mechanism of action, [25][26][27][28] studies on this subject are limited. Upregulation of…”

Section: )mentioning

confidence: 99%

“…24) However, the mechanism underlying the positive effects of SGLT2 inhibitors on pancreatic β-cell preservation has not been fully investigated. Although the attenuation of oxidative stress in pancreatic islet cells by SGLT2 inhibitors is a possible mechanism of action, [25][26][27][28] studies on this subject are limited. Upregulation of α-cell mass has recently been reported as a possible primary driving force of hyperglycemia in T2DM 29,30) ; however, to our knowledge, the effect of SGLT2 inhibitors on α-cell mass or number has not been investigated.…”

Section: )mentioning

confidence: 99%

Protective Effect of Ipragliflozin on Pancreatic Islet Cells in Obese Type 2 Diabetic db/db Mice

Takasu

Takakura

2018

Biological & Pharmaceutical Bulletin

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Ipragliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that increases urinary glucose excretion and subsequently improves hyperglycemia in patients with type 2 diabetes mellitus (T2DM). To assess the beneficial effect of ipragliflozin on the mass and function of pancreatic β-cells under diabetic conditions, obese T2DM db/db mice were treated with ipragliflozin for 5 weeks. Glucose and lipid metabolism parameters, pathological changes in pancreatic islet cells and insulin content were evaluated. Pathological examination of pancreatic islet cells comprised measuring the ratios of insulin-and glucagon-positive cells and levels of oxidative stress markers. Hemoglobin A1c, plasma glucose, non-esterified fatty acid and triglyceride levels in ipragliflozin-treated groups were reduced compared to the diabetic control (DM-control) group. Histopathological examination of pancreatic islet cells revealed strong insulin staining and reduced glucagon staining in the ipragliflozin 10 mg/kg-treated group compared with the DM-control group. The ratio of α-to β-cell mass was lower in the ipragliflozin 10 mg/kg-treated group than the DM-control group and was similar to that of the non-diabetic control group. The density of immunostaining for 4-hydroxy-2-nonenal, an oxidative stress marker, in pancreatic islets was significantly lower in the ipragliflozin 10 mg/kg-treated group than the DM-control group. Pancreatic insulin content tended to be higher in the ipragliflozin-treated groups than the DM-control group. Our findings demonstrate the benefit of ipragliflozin treatment in improving glucolipotoxicity and reducing oxidative stress in pancreatic islet cells. Treatment with ipragliflozin may protect against the progressive loss of islet β-cells in patients with T2DM.Key words ipragliflozin; sodium glucose cotransporter 2 inhibitor; anti-diabetic drug; pancreatic islet cell; type 2 diabetes mellitus Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease. The main characteristics of T2DM are insulin resistance in insulin target tissues and insufficient insulin secretion from pancreatic β-cells.1,2) Insulin resistance develops as a result of overeating, physical inactivity and as a consequence of obesity and fat accumulation in the body caused by excessive insulin secretion from pancreatic β-cells.3) In the prediabetic state, a sufficient amount of insulin is secreted from β-cells to compensate for insulin resistance.4) Subsequently, larger adipocytes accumulate in adipose tissue and secrete large amounts of free fatty acids (FFAs) and inflammatory cytokines, which leads to a deterioration in β-cell function. This process is well known as β-cell lipotoxicity.5) After the collapse of compensatory insulin secretion mechanisms, β-cells are chronically exposed to hyperglycemia, leading to a gradual deterioration in function and decrease in β-cell mass. These phenomena are well known as β-cell glucose toxicity. [6][7][8] Several studies have suggested that increased FFA concentration and hyperglycemia...

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Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice

Cited by 31 publications

References 35 publications

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Hepatic rhythmicity of endoplasmic reticulum stress is disrupted in perinatal and adult mice models of high-fat diet-induced obesity

Protective Effect of Ipragliflozin on Pancreatic Islet Cells in Obese Type 2 Diabetic db/db Mice

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