Synergetic Effects of Prenatal and Postnatal High Sucrose Intake on Glucose Tolerance and Hepatic Insulin Resistance in Rat Offspring

2018 ◽  
Vol 62 (5) ◽  
pp. 1700771 ◽  
Author(s):  
Pengjie Zhang ◽  
Di Zhu ◽  
Yueming Zhang ◽  
Lingjun Li ◽  
Xionghui Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Hepatic Insulin Resistance ◽  
Sucrose Intake ◽  
Rat Offspring ◽  
Synergetic Effects ◽  
High Sucrose

Whole body insulin resistance in rat offspring of mothers consuming alcohol during pregnancy or lactation: comparing prenatal and postnatal exposure

2004 ◽  
Vol 96 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Li Chen ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Glucose Tolerance ◽  
The Body ◽  
Whole Body ◽  
Glucose Disposal ◽  
Tolerance Index ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Rat Offspring

This study examined the effects of maternal ethanol (EtOH) consumption during pregnancy or lactation on glucose homeostasis in the adult rat offspring. Glucose disposal was determined by minimal model during an intravenous glucose tolerance test in rats that had a small or normal birth weight after EtOH exposure in utero and in rats whose mothers were given EtOH during lactation only. All three EtOH groups had decreased glucose tolerance index and insulin sensitivity index, but their glucose effectiveness was not different from that of controls. In addition, EtOH rat offspring that were small at birth had elevated plasma, liver, and muscle triglyceride levels. The data show that EtOH exposure during pregnancy programs the body to insulin resistance later in life, regardless of birth weight, but that this effect also results in dyslipidemia in growth-restricted rats. In addition, insulin resistance is also evident after EtOH exposure during lactation.

Abstract 94: High Sucrose Intake-induced Endoplasmic Reticulum Stress, Inflammation and Fibrosis in hte Pancreas: Role of Trpv1

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Donna H Wang ◽  
Beihua Zhong
Keyword(s):  
Endoplasmic Reticulum ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Impaired Glucose Tolerance ◽  
Insulin Release ◽  
Transient Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Sucrose Intake ◽  
Trpv1 Channels ◽  
High Sucrose

Excessive consumption of sugar may serve as a primary and independent factor for increased morbidity of diabetes. We test the hypothesis that the transient receptor potential vanilloid type 1 (TRPV1) channels play a protective role against sugar-induced pancreatic endoplasmic reticulum (ER) stress, inflammatory cell infiltration, and tissue fibrosis. Wild-type (WT, C57BL/6) or gene-targeted TRPV1-null mutant (TRPV1 -/- ) mice were fed a normal (CON) or high sucrose diet for 22-23 weeks. TRPV1 ablation impaired glucose tolerance and suppressed glucose-induced insulin release when fed a CON diet (p<0.05). Sucrose intake further impaired glucose tolerance and insulin release in TRPV1 -/- compared to WT mice (p<0.05). Sucrose intake increased pancreatic ER stress, showing elevated levels of chop protein content in both strains and GRP78, XBP-1, and CREB-2 in TRPV1 -/- mice only (p<0.05). TRPV1 ablation increased levels of phosphorylated JNK (WT, 0.12±0.14; TRPV1-/-, 0.31±0.13) and decreased glut2 contents (WT, 1.38±0.24; TRPV1-/-, 0.83±0.09) in the pancreas when fed a CON diet (p<0.05). Sucrose intake further increased levels of pancreatic phosphorylated JNK (WT, 0.89±0.19; TRPV1-/-, 1.05±0.19) and decreased glut2 contents (WT, 0.39±0.04; TRPV1-/-, 0.26±0.16) in both strains (p<0.05). Sucrose intake increased pancreatic TGF-β levels in both strains with exacerbation in TRPV1-/- mice (p<0.05), and increased pancreatic phosphorylated Smad2/3 and collagen levels in TRPV1 -/- mice only (p<0.05). Quantitative immunostaining revealed that sucrose intake enhanced pancreatic infiltration of CD3 positive cells in both strains and macrophage in TRPV1 -/- mice only (p<0.05). Thus, TRPV1 ablation impairs insulin release and glucose tolerance at baseline possibly via increased pancreatic phosphorylated JNK signaling and decreased glut2 expression. Sucrose intake aggravates impairment in insulin release and glucose tolerance when TRPV1 is ablation, possibly via enhancing ER stress, macrophage infiltration, and activation of the TGF-β/Smad pathway leading to pancreatic fibrosis, suggesting preserving TRPV1 expression and function may attenuate pancreatic injury via alleviating inflammatory responses.

scholarly journals Ceramide Content in Liver Increases Along with Insulin Resistance in Obese Patients

2019 ◽  
Vol 8 (12) ◽  
pp. 2197 ◽  
Author(s):  
Hady Razak Hady ◽  
Agnieszka U. Błachnio-Zabielska ◽  
Łukasz Szczerbiński ◽  
Piotr Zabielski ◽  
Monika Imierska ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Glycosylated Hemoglobin ◽  
Hepatic Insulin Resistance ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Obese Patients ◽  
Men And Women ◽  
Percentage Body Fat ◽  
Ceramide Content

The liver plays a central role in the glucose and lipid metabolism. Studies performed on animal models have shown an important role of lipid accumulation in the induction of insulin resistance. We sought to explain whether in obese humans, the insulin resistance is associated with hepatic ceramide accumulation. The experiments were conducted on obese men and women. Each gender was divided into three groups: Normal glucose tolerance group (NGT), Impaired glucose tolerance group (IGT), and Type 2 diabetic subjects (T2D). Ceramide (Cer) content was analyzed with the use of LC/MS/MS. An oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1c), percentage body fat (FAT%), and body mass index (BMI) was also measured. Total hepatic ceramide was significantly higher in T2D females as compared to NGT females (p < 0.05), whereas in males, total ceramide was significantly higher in IGT and T2D as compared to NGT (p < 0.05). In both, men and women, the highest increase in T2D subjects, was observed in C16:0-Cer, C18:0:-Cer, C22:0-Cer, and C24:0-Cer (p < 0.05) as compared to NGT group. Interestingly, glucose (at 0′ and at 120′ in OGTT) and HbA1c positively correlated with the ceramide species that most increased in T2D patients (C16:0-Cer, C18:0-Cer, C22:0-Cer, and C24:0-Cer). In men glucose and HbA1c significantly correlated with only C22:0-Cer. This is one of the few studies comparing hepatic ceramide content in severely obese patients. We found that, ceramide content increased in diabetic patients, both in men and women, and the content of ceramide correlated with glycemic parameters. These data indicate ceramide contribution to the induction of hepatic insulin resistance.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21

2012 ◽  
Vol 167 (3) ◽  
pp. 301-309 ◽  
Author(s):  
Pedro Iglesias ◽  
Rafael Selgas ◽  
Sara Romero ◽  
Juan J Díez
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Growth Factor ◽  
Glucose Tolerance ◽  
Hepatic Insulin Resistance ◽  
Fibroblast Growth Factor 21 ◽  
Diabetic Patients ◽  
Glucose Transporter 1 ◽  
Insulin Resistant ◽  
The Metabolic Syndrome

Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.

Increased net hepatic glucose output from gluconeogenic precursors after high-sucrose diet feeding in male rats

1997 ◽  
Vol 272 (2) ◽  
pp. R526-R531 ◽  
Author(s):  
M. J. Pagliassotti ◽  
P. A. Prach
Keyword(s):  
Insulin Resistance ◽  
Glucose Production ◽  
Male Rats ◽  
Hepatic Insulin Resistance ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
Glucose Output ◽  
High Sucrose

A high-sucrose diet reduces the ability of insulin to suppress hepatic glucose production (hepatic insulin resistance) in rats. The purpose of the present study was to investigate the contribution of hepatic gluconeogenesis to sucrose-induced hepatic insulin resistance. Single-pass liver perfusions were performed on 24-h food-deprived male Wistar rats after 8 wk on either a high-corn starch (ST; 68% of energy) or high-sucrose (SU; 68% of energy) diet. Hepatic glucose output (HGO, micromol of glucose x min(-1) x g(-1)) in the presence of lactate, alanine, or dihydroxyacetone (DHA) was used as an estimate of gluconeogenic capacity, because liver glycogen levels after the 24-h fast were negligible (<1.2 mg/g). HGO was significantly (P < 0.05) greater in SU vs. ST at all concentrations of lactate, alanine, and DHA. Maximal rates of HGO were 1.9 +/- 0.4 and 2.8 +/- 0.3 at 10 mM lactate, 0.6 +/- 0.2 and 1.4 +/- 0.3 at 10 mM alanine, and 1.7 +/- 0.3 and 2.6 +/- 0.2 at 20 mM DHA in ST and SU, respectively. When HGO was matched between SU and ST with the use of different precursor concentrations, there was a significant (P < 0.05) reduction in the ability of insulin (175 microU/ml) to suppress HGO in SU vs. ST. These data suggest that sucrose feeding increases gluconeogenesis from lactate, alanine, and DHA and that this route of glucose production is resistant to insulin suppression.

Retinol-binding protein 4 is associated with impaired glucose tolerance but not with whole body or hepatic insulin resistance in Mexican Americans

2009 ◽  
Vol 296 (4) ◽  
pp. E758-E764 ◽  
Author(s):  
Alberto O. Chavez ◽  
Dawn K. Coletta ◽  
Subhash Kamath ◽  
Douglas T. Cromack ◽  
Adriana Monroy ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Mexican Americans ◽  
Hepatic Glucose Production ◽  
Retinol Binding Protein ◽  
Hepatic Insulin Resistance ◽  
Whole Body

Retinol-binding protein-4 (RBP4), a novel protein secreted mainly by adipose tissue, has been associated with insulin resistance in obese subjects and in individuals with type 2 diabetes mellitus (T2DM). We examined the relationship between plasma RBP4 levels, expression of RBP4 in skeletal muscle and adipose tissue, and insulin sensitivity in Mexican Americans with varying degrees of obesity and glucose tolerance. Seventy-two subjects [16 lean normal-glucose-tolerant (NGT), 17 obese NGT, and 39 subjects with impaired fasting glucose/impaired glucose tolerance/T2DM] received an oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Insulin secretion was measured as insulinogenic index during OGTT. In a subset of subjects, hepatic glucose production was measured by 3-[3H]glucose infusion, biopsies of the vastus lateralis muscle and subcutaneous adipose tissue were obtained under basal conditions, and quantitative RT-PCR was performed to measure the RBP4 mRNA gene expression. Plasma RBP4 was significantly elevated in impaired glucose tolerance/T2DM compared with NGT lean or obese subjects. Plasma RBP4 levels correlated with 2-h glucose, triglycerides, and hemoglobin A1c. There was no association between RBP4 levels and whole body insulin sensitivity measured with either the euglycemic insulin clamp or OGTT, basal hepatic glucose production rates, and the hepatic insulin resistance index. There was no correlation between plasma RBP4 levels and indexes of insulin secretion. RBP4 mRNA expression in skeletal muscle was similar in lean NGT subjects, obese NGT subjects, and T2DM subjects. There was no difference in RBP4 mRNA expression in adipose tissue between lean and obese NGT subjects or between NGT and T2DM individuals. Plasma RBP4 levels are elevated in T2DM and associated with impaired glucose tolerance, but not associated with obesity or insulin resistance or impaired insulin secretion in Mexican Americans.

ZFAND3 Overexpression in the Mouse Liver Improves Glucose Tolerance and Hepatic Insulin Resistance

2021 ◽  
Author(s):  
Kahori Shimizu ◽  
Yuya Ogiya ◽  
Kaede Yoshinaga ◽  
Hajime Kimura ◽  
Shotaro Michinaga ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Mouse Liver ◽  
Hepatic Insulin Resistance ◽  
Genome Wide Association Studies ◽  
Primary Mouse

AbstractGenome-wide association studies have identified more than 300 loci associated with type 2 diabetes mellitus; however, the mechanisms underlying their role in type 2 diabetes mellitus susceptibility remain largely unknown. Zinc finger AN1-type domain 3 (ZFAND3), known as testis-expressed sequence 27, is a type 2 diabetes mellitus-susceptibility gene. Limited information is available regarding the physiological role of ZFAND3 in vivo. This study aimed to investigate the association between ZFAND3 and type 2 diabetes mellitus. ZFAND3 was significantly upregulated in the liver of diabetic mice compared to wild-type mice. To overexpress ZFAND3, we generated a ZFAND3-expressing adenovirus (Ad) vector using an improved Ad vector exhibiting significantly lower hepatotoxicity (Ad-ZFAND3). Glucose tolerance was significantly improved in Ad-ZFAND3-treated mice compared to the control Ad-treated mice. ZFAND3 overexpression in the mouse liver also improved insulin resistance. Furthermore, gluconeogenic gene expression was significantly lower in primary mouse hepatocytes transduced with Ad-ZFAND3 than those transduced with the control Ad vector. The present results suggest that ZFAND3 improves glucose tolerance by improving insulin resistance and suppressing gluconeogenesis, serving as a potential novel therapeutic target for type 2 diabetes mellitus.

Effect of KCNH6 on Hepatic Endoplasmic Reticulum Stress and Glucose Metabolism

2020 ◽  
Vol 52 (09) ◽  
pp. 669-675
Author(s):  
Jing Lu ◽  
Han Shen ◽  
Qi Li ◽  
Feng-Ran Xiong ◽  
Ming-Xia Yuan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Hepatic Insulin Resistance ◽  
Glucose Metabolism Disorders ◽  
Primary Hepatocytes ◽  
Iκb Kinase

AbstractAdult patients with a dysfunctional ether-a-go-go 2 (hERG2) protein, which is encoded by the KCNH6 gene, present with hyperinsulinemia and hyperglycemia. However, the mechanism of KCNH6 in glucose metabolism disorders has not been clearly defined. It has been proposed that sustained endoplasmic reticulum (ER) stress is closely concerned with hepatic insulin resistance and inflammation. Here, we demonstrate that Kcnh6 knockout (KO) mice had impaired glucose tolerance and increased levels of hepatic apoptosis, in addition to displaying an increased insulin resistance that was mediated by high ER stress levels. By contrast, overexpression of KCNH6 in primary hepatocytes led to a decrease in ER stress and apoptosis induced by thapsigargin. Similarly, induction of Kcnh6 by tail vein injection into KO mice improved glucose tolerance by reducing ER stress and apoptosis. Furthermore, we show that KCNH6 alleviated hepatic ER stress, apoptosis, and inflammation via the NFκB-IκB kinase (IKK) pathway both in vitro and in vivo. In summary, our study provides new insights into the causes of ER stress and subsequent induction of primary hepatocytes apoptosis.

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