Interactions between effects of adrenalectomy and diet on insulin secretion in fa/fa Zucker rats

2001 ◽  
Vol 79 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Molly T Kibenge ◽  
Catherine B Chan
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Weight Gain ◽  
Cell Function ◽  
Cafeteria Diet ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Oral Glucose

Our objective was to determine if a cafeteria-type diet with increased fat content would block the decrease in insulin secretion induced by adrenalectomy in obese rats. Five week old Zucker (fa/fa) rats were adrenalectomized. One week later, half of the adrenalectomized groups, and age-matched, sham-operated animals were given a diet of 16% fat and 44% carbohydrate. Control animals were maintained on standard rat chow (4.6% fat and 49% carbohydrate). After 4 weeks on the diets, in vivo measurements included caloric intake, weight gain, plasma corticosterone, triglyceride, free fatty acids, and oral glucose tolerance tests. In vitro measurements included glucose-stimulated insulin secretion, glucose phosphorylating activity, islet triglyceride content, and fatty acid oxidizing activity of cultured islets. Generally, the cafeteria diet did not block the effects of adrenalectomy on in vitro insulin secretion parameters, even though in sham-operated animals weight gain and insulin resistance was induced by the diet in vivo. Adrenalectomy and the diet exerted independent effects on glucose phosphorylation and fatty acid oxidation in islets. In conclusion, adrenalectomy decreased the elevated insulin secretion in fa/fa rats. The failure of a cafeteria diet enriched in fat to block the adrenalectomy-mediated changes in B-cell function indicates the importance of glucocorticoids and centrally-mediated effects on insulin secretion and other metabolic parameters.Key words: obesity, insulin secretion, islets of Langerhans, adrenalectomy, high fat diet.

Voluntary running exercise prevents β-cell failure in susceptible islets of the Zucker diabetic fatty rat

2012 ◽  
Vol 302 (2) ◽  
pp. E254-E264 ◽  
Author(s):  
Viviane Delghingaro-Augusto ◽  
Simon Décary ◽  
Marie-Line Peyot ◽  
Martin G. Latour ◽  
Julien Lamontagne ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Secretion ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cell Function ◽  
Acid Oxidation ◽  
Oral Glucose ◽  
Β Cell ◽  
Voluntary Running ◽  
Zdf Rats

Physical activity improves glycemic control in type 2 diabetes (T2D), but its contribution to preserving β-cell function is uncertain. We evaluated the role of physical activity on β-cell secretory function and glycerolipid/fatty acid (GL/FA) cycling in male Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats engaged in voluntary running for 6 wk (ZDF-A). Inactive Zucker lean and ZDF (ZDF-I) rats served as controls. ZDF-I rats displayed progressive hyperglycemia with β-cell failure evidenced by falling insulinemia and reduced insulin secretion to oral glucose. Isolated ZDF-I rat islets showed reduced glucose-stimulated insulin secretion expressed per islet and per islet protein. They were also characterized by loss of the glucose regulation of fatty acid oxidation and GL/FA cycling, reduced mRNA expression of key β-cell genes, and severe reduction of insulin stores. Physical activity prevented diabetes in ZDF rats through sustaining β-cell compensation to insulin resistance shown in vivo and in vitro. Surprisingly, ZDF-A islets had persistent defects in fatty acid oxidation, GL/FA cycling, and β-cell gene expression. ZDF-A islets, however, had preserved islet insulin mRNA and insulin stores compared with ZDF-I rats. Physical activity did not prevent hyperphagia, dyslipidemia, or obesity in ZDF rats. In conclusion, islets of ZDF rats have a susceptibility to failure that is possibly due to altered β-cell fatty acid metabolism. Depletion of pancreatic islet insulin stores is a major contributor to islet failure in this T2D model, preventable by physical activity.

Blood flow to brown fat in lean and obese adrenalectomized Zucker rats

1986 ◽  
Vol 251 (5) ◽  
pp. R851-R858
Author(s):  
S. J. Wickler ◽  
B. A. Horwitz ◽  
J. S. Stern
Keyword(s):  
Blood Flow ◽  
Weight Gain ◽  
Brown Fat ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Nonshivering Thermogenesis ◽  
Brown Adipose ◽  
Obese Rats

The Zucker obese rat is characterized by decreased capacity for diet-induced and for nonshivering thermogenesis. This decrease is due, in large part, to reduced thermogenesis in depots of brown adipose tissue, a major source of heat production in rats. Adrenalectomy retards the weight gain observed in the obese rats and also normalizes brown fat guanosine 5'-diphosphate (GDP) binding, an in vitro measure of brown fat thermogenic capacity. This study examined the effect of adrenalectomy on brown fat blood flow, an in vivo measure of the tissue's function, and on norepinephrine-induced O2 consumption (NST) of 11-wk-old obese (fa/fa) and lean (Fa/?) rats. Adrenalectomy had little effect on weight gain, NST, or norepinephrine-stimulated blood flow to brown fat in lean rats. However, adrenalectomy produced profound changes in the obese animals, preventing the weight gain normally occurring in the obese rats and normalizing both NST capacity and norepinephrine-stimulated blood flow to brown fat. These findings provide further support for the importance of brown fat thermogenesis and glucocorticoids in modulating the obesity of the Zucker rat.

scholarly journals Critical Role for Hepatocyte-Specific eNOS in NAFLD and NASH

2021 ◽  
Author(s):  
Rory P. Cunningham ◽  
Mary P. Moore ◽  
Ryan J. Daskek ◽  
Grace M. Meers ◽  
Takamune Takahashi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Critical Role ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Fatty Acid ◽  
Endothelial Nitric Oxide

Regulation of endothelial nitric oxide synthase (eNOS) in hepatocytes may be an important target in nonalcoholic fatty liver disease (NAFLD) development and progression to steatohepatitis (NASH). In this study, we show genetic deletion and viral knockdown of hepatocyte-specific eNOS exacerbated hepatic steatosis and inflammation, decreased hepatic mitochondrial fatty acid oxidation and respiration, increased mitochondrial H<sub>2</sub>O<sub>2</sub> emission, and impaired the hepatic mitophagic (BNIP3 and LC3II) response. Conversely, overexpressing eNOS in hepatocytes in vitro and in vivo increased hepatocyte mitochondrial respiration and attenuated western diet induced NASH. Moreover, patients with elevated NAFLD activity score (histology score of worsening steatosis, hepatocyte ballooning, and inflammation) exhibited reduced hepatic eNOS expression which correlated with reduced hepatic mitochondrial fatty acid oxidation and lower hepatic protein expression of mitophagy protein BNIP3. The current study reveals an important molecular role for hepatocyte-specific eNOS as a key regulator of NAFLD/NASH susceptibility and mitochondrial quality control with direct clinical correlation to patients with NASH.

scholarly journals Pomegranate vinegar feeding enhances fatty acid oxidation: In vitro and in vivo

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
YEOJIN PARK ◽  
Elly Ok ◽  
Hyo Jung Lee ◽  
Ji Yeon Kim ◽  
Mi Kyung Kim ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation

Abstract 344: FNDC5, a PGC1-a-Dependent Myokine, Increases Glucose Utilization and Fatty-Acid Oxidation by AMPK Signaling Pathway

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ling Tao ◽  
Yi Liu ◽  
Chao Xin ◽  
Weidong Huang ◽  
Lijian Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
C2c12 Cells ◽  
Time Dependent ◽  
Acid Oxidation ◽  
Ampk Signaling

FNDC5 is a hormone secreted by myocytes that could reduce obesity and insulin resistance, However, the exact effect of FNDC5 on glucose and lipid metabolism remain poorly identified; More importantly, the signaling pathways that mediate the metabolic effects of FNDC5 is completely unknown. Here we showed that FNDC5 stimulates β-oxidation and glucose uptake in C2C12 cells in a dose- and time-dependent fashion in vitro (n=8, all P<0.01). In vivo study revealed that FNDC5 also enhanced glucose tolerance in diabetic mice and increased the glucose uptake evidenced by increased [18F] FDG accumulation in hearts by PET scan (n=6, all P<0.05). FNDC5 decreased the expression of gluconeogenesis related molecules (PEPCK and G6Pase) and increased the phosphorylation of ACC, a key modulator of fatty-acid oxidation, both in hepatocytes and C2C12 cells (n=3, all P<0.05). In parallel with its stimulation of β-oxidation and glucose uptake, FNDC5 increased the phosphorylation of AMPK both in hepatocytes and C2C12 cells in a dose- and time-dependent fashion in vitro and in vivo. More importantly, the β-oxidation and glucose uptake, the expression of PEPCK and G6Pase and the phosphorylation of ACC induced by FNDC5 were attenuated by AMPK inhibitor in hepatocytes and C2C12 cells (P<0.05). Most importantly, the FNDC5 induced glucose uptake and phosphorylation of ACC were attenuated in AMPK-DN mice (n=6, all P<0.05). The glucose-lowering effect of FNDC5 in diabetic mice was also attenuated by AMPK inhibitor. Our data presents the direct evidence that FNDC5 stimulates glucose utilization and fatty-acid oxidation by AMPK signaling pathway, suggesting that FNDC5 be a novel pharmacological approach for type 2 diabetes.

scholarly journals A Combination of Caffeine, Arginine, Soy Isoflavones, and l-Carnitine Enhances Both Lipolysis and Fatty Acid Oxidation in 3T3-L1 and HepG2 Cells in Vitro and in KK Mice in Vivo

2007 ◽  
Vol 137 (10) ◽  
pp. 2252-2257 ◽  
Author(s):  
Shinji Murosaki ◽  
Tae Ryong Lee ◽  
Koutarou Muroyama ◽  
Eui Seok Shin ◽  
Si Young Cho ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Hepg2 Cells ◽  
Soy Isoflavones ◽  
Acid Oxidation ◽  
Kk Mice

Effect of gestational hyperglycemia on insulin secretion in vivo and in vitro by fetal rat pancreas

1986 ◽  
Vol 251 (1) ◽  
pp. E86-E91 ◽  
Author(s):  
M. T. Bihoreau ◽  
A. Ktorza ◽  
A. Kervran ◽  
L. Picon
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
Insulin Release ◽  
Plasma Insulin ◽  
Cell Function ◽  
Pregnant Rats ◽  
Fetal Rat ◽  
Gestational Hyperglycemia

The effects of gestational hyperglycemia on B-cell function were studied in near-term fetuses from unrestrained pregnant rats made slightly or highly hyperglycemic using continuous glucose infusion during the last week of pregnancy. Pancreatic and plasma insulin and insulin secretion in vitro were studied in the fetuses. Compared with controls, slightly hyperglycemic fetuses showed increased pancreatic and plasma insulin concentrations and similar insulin release in response to glucose in vitro. In highly hyperglycemic fetuses, pancreatic and plasma insulin concentrations were unchanged compared with controls, and insulin release in vitro was insensitive to glucose and to the mixture glucose plus theophylline. These results confirm that glucose is able to stimulate insulin secretion in normal or slightly hyperglycemic fetuses and suggest that severe hyperglycemia per se, without association of other metabolic disorders or toxic injuries, profoundly alters the stimulus-secretion coupling of the fetal rat B-cell.

scholarly journals High Glucose Aggravates the Detrimental Effects of Pancreatic Stellate Cells on Beta-Cell Function

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Min Zha ◽  
Wei Xu ◽  
Qing Zhai ◽  
Fengfei Li ◽  
Bijun Chen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
High Glucose ◽  
Cell Function ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
High Concentration ◽  
Gk Rats ◽  
Chop Expression

Background and Aims. We here assess the effects of PSCs onβ-cell function and apoptosisin vivoandin vitro.Materials and Methods.PSCs were transplanted into Wistar and Goto-Kakizaki (GK) rats. Sixteen weeks after transplantation,β-cell function, apoptosis, and islet fibrosis were assessed.In vitrothe effects of PSCs conditioned medium (PSCs-CM) and/or high concentration of glucose on INS-1 cell function was assessed by measuring insulin secretion, INS-1 cell survival, apoptosis, and endoplasmic reticulum stress (ER stress) associated CHOP expression.Results. PSCs transplantation exacerbated the impairedβ-cell function in GK rats, but had no significant effects in Wistar rats.In vitro, PSCs-CM caused impaired INS-1 cell viability and insulin secretion and increased apoptosis, which were more pronounced in the presence of high glucose.Conclusion.Our study demonstrates that PSCs induceβ-cell failurein vitroandin vivo.

scholarly journals Critical Role for Hepatocyte-Specific eNOS in NAFLD and NASH

2021 ◽  
Author(s):  
Rory P. Cunningham ◽  
Mary P. Moore ◽  
Ryan J. Daskek ◽  
Grace M. Meers ◽  
Takamune Takahashi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Critical Role ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Fatty Acid ◽  
Endothelial Nitric Oxide

Regulation of endothelial nitric oxide synthase (eNOS) in hepatocytes may be an important target in nonalcoholic fatty liver disease (NAFLD) development and progression to steatohepatitis (NASH). In this study, we show genetic deletion and viral knockdown of hepatocyte-specific eNOS exacerbated hepatic steatosis and inflammation, decreased hepatic mitochondrial fatty acid oxidation and respiration, increased mitochondrial H<sub>2</sub>O<sub>2</sub> emission, and impaired the hepatic mitophagic (BNIP3 and LC3II) response. Conversely, overexpressing eNOS in hepatocytes in vitro and in vivo increased hepatocyte mitochondrial respiration and attenuated western diet induced NASH. Moreover, patients with elevated NAFLD activity score (histology score of worsening steatosis, hepatocyte ballooning, and inflammation) exhibited reduced hepatic eNOS expression which correlated with reduced hepatic mitochondrial fatty acid oxidation and lower hepatic protein expression of mitophagy protein BNIP3. The current study reveals an important molecular role for hepatocyte-specific eNOS as a key regulator of NAFLD/NASH susceptibility and mitochondrial quality control with direct clinical correlation to patients with NASH.

scholarly journals Perilipin2 down-regulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria

2020 ◽  
Author(s):  
Akansha Mishra ◽  
Siming Liu ◽  
Joseph Promes ◽  
Mikako Harata ◽  
William Sivitz ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Islet Cells ◽  
Cell Metabolism ◽  
Nutritional Stress ◽  
Β Cells ◽  
Β Cell ◽  
Down Regulation

Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in β cells that increases under nutritional stress. Down-regulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was down-regulated in mouse β cells, INS1 cells, and human islet cells. β cell specific deletion of PLIN2 in mice on a high fat diet reduced glucose-stimulated insulin secretion (GSIS) in vivo and in vitro. Down-regulation of PLIN2 in INS1 cells blunted GSIS after 24 h incubation with 0.2 mM palmitic acids. Down-regulation of PLIN2 in human pseudoislets cultured at 5.6 mM glucose impaired both phases of GSIS, indicating that PLIN2 is critical for GSIS. Down-regulation of PLIN2 decreased specific OXPHOS proteins in all three models and reduced oxygen consumption rates in INS1 cells and mouse islets. Moreover, we found that PLIN2 deficient INS1 cells increased the distribution of a fluorescent oleic acid analog to mitochondria and showed signs of mitochondrial stress as indicated by susceptibility to fragmentation and alterations of acyl-carnitines and glucose metabolites. Collectively, PLIN2 in β cells have an important role in preserving insulin secretion, β cell metabolism and mitochondrial function under nutritional stress.

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