Chronic malnutrition impairs insulin sensitivity through both receptor and postreceptor defects in rats with mild streptozocin diabetes

Rao, R. Govinda; Menon, Ram K.

doi:10.1016/0026-0495(93)90248-m

Cited by 13 publications

(3 citation statements)

References 30 publications

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“…Several studies have attempted to characterize the molecular mechanisms underlying the impaired response of the pancreatic islets of protein-deficient animals to glucose and other insulinotrophic agents (Rao & Menon 1993, Reis et al 1997, Latorraca et al 1998, Barbosa et al 2002, Ferreira et al 2003. Caloric and protein deficiency produce phenotypic changes in pancreatic islets, which are smaller and composed of a lower number of -cells, than islets of eutrophic animals (Petrik et al 2001).…”

Section: Figurementioning

confidence: 99%

Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2

Araujo

Amaral²,

Filiputti³

et al. 2004

Journal of Endocrinology

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Autocrine and paracrine insulin signaling may participate in the fine control of insulin secretion. In the present study, tissue distribution and protein amounts of the insulin receptor and its major substrates, insulin receptor substrate (IRS)-1 and IRS-2, were evaluated in a model of impaired glucose-induced insulin secretion, the proteindeficient rat. Immunoblot and RT-PCR studies showed that the insulin receptor and IRS-2 expression are increased, whilst IRS-1 protein and mRNA contents are decreased in pancreatic islets of protein-deficient rats. Immunohistochemical studies revealed that the insulin receptor and IRS-1 and -2 are present in the great majority of islet cells; however, the greatest staining was localized at the periphery, suggesting a co-localization with non-insulin-secreting cells. Exogenous insulin stimulation of isolated islets promoted higher insulin receptor and IRS-1 and -2 tyrosine phosphorylation in islets from protein-deficient rats, as compared with controls. Moreover, insulin-induced IRS-1-and IRS-2-associated phosphatidylinositol 3-kinase activity are increased in islets of protein-deficient rats. The reduction of IRS-1 and IRS-2 protein expression in islets isolated from proteindeficient rats by the use of antisense IRS-1 or IRS-2 phosphorthioate-modified oligonucleotides partially restored glucose-induced insulin secretion. Thus, the impairment of insulin cell signaling through members of the IRS family of proteins in isolated rat pancreatic islets improves glucose-induced insulin secretion. The present data reinforced the role of insulin paracrine and autocrine signaling in the control of its own secretion.

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Section: Figurementioning

confidence: 99%

Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2

Araujo

Amaral²,

Filiputti³

et al. 2004

Journal of Endocrinology

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“…In addition, the increased glucagon‐to‐insulin ratio in the plasma of fetuses of food‐restricted rats (Girard et al 1977) influences the activity of glycolytic and gluconeogenic enzymes in the liver: the glucokinase activity was found to be lower and the phosphoenolpyruvate carboxykinase activity higher in offspring of rats fed a low‐protein diet during gestation (Desai et al 1997). The hypoinsulinaemia at adult age may itself be involved: insulin resistance in the liver was reported in mildly diabetic rats subjected to long‐term malnutrition (Rao & Menon, 1993).…”

Section: Animal Modelsmentioning

confidence: 99%

Lifetime consequences of abnormal fetal pancreatic development

2003

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There is ample evidence that an adverse intrauterine environment has harmful consequences for health in later life. Maternal diabetes and experimentally induced hyperglycaemia result in asymmetric overgrowth, which is associated with an increased insulin secretion and hyperplasia of the insulin-producing B-cells in the fetuses. In adult life, a reduced insulin secretion is found. In contrast, intrauterine growth restriction is associated with low insulin secretion and a delayed development of the insulin-producing B-cells. These perinatal alterations may induce a deficient adaptation of the endocrine pancreas and insulin resistance in later life. Intrauterine growth restriction in human pregnancy is mainly due to a reduced uteroplacental blood flow or to maternal undernutrition or malnutrition. However, intrauterine growth restriction can be present in severe diabetes complicated by vasculopathy and nephropathy. In animal models, intrauterine growth retardation can be obtained through pharmacological (streptozotocin), dietary (semi-starvation, low protein diet) or surgical (intrauterine artery ligation) manipulation of the maternal animal. The endocrine pancreas and more specifically the insulin-producing B-cells play an important role in the adaptation to an adverse intrauterine milieu and the consequences in later life. The long-term consequences of an unfavourable intrauterine environment are of major importance worldwide. Concerted efforts are needed to explore how these long-term effects can be prevented. This review will consist of two parts. In the first part, we discuss the long-term consequences in relation to the development of the fetal endocrine pancreas and fetal growth in the human; in the second part, we focus on animal models with disturbed fetal and pancreatic development and the consequences for later life.

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“…Animal data showed that chronic malnutrition is associated with insulin resistance, both through receptor and post-receptor defects. 26,27 There is limited data in humans in this regard.…”

Section: Discussionmentioning

confidence: 99%

Malnutrition and Metabolic Changes in Patients with Type 2 Diabetes

Roiban

Both²

2018

Journal of Interdisciplinary Medicine

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Background/Aim: In patients with type 2 diabetes (T2D), malnutrition has been recognized as a serious health problem mainly in hospitalized conditions, but there is little data regarding malnutrition outside hospital settings. The aim of this study was to evaluate the risk of malnutrition and associated metabolic changes in ambulatory patients with T2D. Material and methods: This analysis used data collected from 161 patients with T2D enrolled in a larger crosssectional study. Several anthropometric and metabolic parameters were obtained. Nutritional status was evaluated using the Controlling Nutritional Status (CONUT) score. Correlations between nutritional status and metabolic and anthropometric parameters of interest were examined. Results: Of all T2D patients, 29.8% had mild malnutrition (CONUT score 2-4). These patients presented lower triglyceride (124.8 ± 42.3 mg/dL vs. 165.7 ± 84.3 mg/dL, p <0.01) and LDL cholesterol concentrations (62.7 ± 20.0 mg/dL vs. 104.9 ± 30.6 mg/dL, p <0.0001), higher leptin levels (10.2 [1.6-44.9] ng/mL vs. 7.3 [0.9-49.8] ng/mL, p <0.05) and free leptin index (0.65 [0.04-2.88] vs. 0.36 [0.01-3.98], p <0.05) compared with patients with normal nutritional status. They also had higher total body adiposity. In patients with obesity, triglycerides levels were lower in those with mild malnutrition vs. those without malnutrition (mean difference: 27.26 mg/ dL, p <0.05). Serum C peptide/leptin ratio was higher in T2D patients with normal nutritional status without obesity, the differences being significant vs. the two groups with obesity (with or without malnutrition, 0.71 ± 0.53, 0.42 ± 0.33, and 0.49 ± 0.68, respectively). HOMA-IR was lower in patients with normal nutritional status without obesity vs. those with obesity (mean difference: -0.7126, p <0.05), while in patients with mild malnutrition, HOMA-IR values were higher, but no differences were noted between the groups with or without obesity. Conclusion: In patients with T2D, malnutrition associated with lower triglycerides concentrations, even in the presence of obesity. Malnutrition and/or obesity associated with higher HOMA-IR, serum leptin levels and lower C peptide/leptin ratio.

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Chronic malnutrition impairs insulin sensitivity through both receptor and postreceptor defects in rats with mild streptozocin diabetes

Cited by 13 publications

References 30 publications

Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2

Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2

Lifetime consequences of abnormal fetal pancreatic development

Malnutrition and Metabolic Changes in Patients with Type 2 Diabetes

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