scholarly journals Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat

2010 ◽  
Vol 299 (3) ◽  
pp. G751-G760 ◽  
Author(s):  
Derek M. Culnan ◽  
Vance Albaugh ◽  
Mingjie Sun ◽  
Christopher J. Lynch ◽  
Charles H. Lang ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Zucker Rats ◽  
Ileal Interposition ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
Glucagon Like Peptide 1

The hindgut hypothesis posits improvements in Type 2 diabetes after gastric bypass surgery are due to enhanced delivery of undigested nutrients to the ileum, which increase incretin production and insulin sensitivity. The present study investigates the effect of ileal interposition (IT), surgically relocating a segment of distal ileum to the proximal jejunum, on glucose tolerance, insulin sensitivity, and glucose transport in the obese Zucker rat. Two groups of obese Zucker rats were studied: IT and sham surgery ad libitum fed (controls). Changes in food intake, body weight and composition, glucose tolerance, insulin sensitivity and tissue glucose uptake, and insulin signaling as well as plasma concentrations of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide were measured. The IT procedure did not significantly alter food intake, body weight, or composition. Obese Zucker rats demonstrated improved glucose tolerance 3 wk after IT compared with the control group ( P < 0.05). Euglycemic, hyperinsulinemic clamp and 1-[14C]-2-deoxyglucose tracer studies indicate that IT improves whole body glucose disposal, insulin-stimulated glucose uptake, and the ratio of phospho- to total Akt ( P < 0.01 vs. control) in striated muscle. After oral glucose, the plasma concentration of glucagon-like peptide-1 was increased, whereas GIP was decreased following IT. Enhanced nutrient delivery to the ileum after IT improves glucose tolerance, insulin sensitivity and muscle glucose uptake without altering food intake, body weight, or composition. These findings support the concept that anatomic and endocrine alterations in gut function play a role in the improvements in glucose homeostasis after the IT procedure.

Sensory nerve inactivation by resiniferatoxin improves insulin sensitivity in male obese Zucker rats

2005 ◽  
Vol 288 (6) ◽  
pp. E1137-E1145 ◽  
Author(s):  
Sophia G. Moesgaard ◽  
Christian L. Brand ◽  
Jeppe Sturis ◽  
Bo Ahrén ◽  
Michael Wilken ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats

Recent studies have suggested that sensory nerves may influence insulin secretion and action. The present study investigated the effects of resiniferatoxin (RTX) inactivation of sensory nerves (desensitization) on oral glucose tolerance, insulin secretion and whole body insulin sensitivity in the glucose intolerant, hyperinsulinemic, and insulin-resistant obese Zucker rat. After RTX treatment (0.05 mg/kg RTX sc given at ages 8, 10, and 12 wk), fasting plasma insulin was reduced ( P < 0.0005), and oral glucose tolerance was improved ( P < 0.005). Pancreas perfusion showed that baseline insulin secretion (7 mM glucose) was lower in RTX-treated rats ( P = 0.01). Insulin secretory responsiveness to 20 mM glucose was enhanced in the perfused pancreas of RTX-treated rats ( P < 0.005) but unaffected in stimulated, isolated pancreatic islets. At the peak of spontaneous insulin resistance in the obese Zucker rat, insulin sensitivity was substantially improved after RTX treatment, as evidenced by higher glucose infusion rates (GIR) required to maintain euglycemia during a hyperinsulinemic euglycemic (5 mU·kg−1·min−1) clamp (GIR60–120min: 5.97 ± 0.62 vs. 11.65 ± 0.83 mg·kg−1·min−1 in RTX-treated rats, P = 0.003). In conclusion, RTX treatment and, hence, sensory nerve desensitization of adult male obese Zucker rats improved oral glucose tolerance by enhancing insulin secretion, and, in particular, by improving insulin sensitivity.

The effects of ovarian hormones on regulation of energy balance in Zucker rats

1983 ◽  
Vol 98 (2) ◽  
pp. 165-171 ◽  
Author(s):  
M. A. Shaw ◽  
E. M. Whitaker ◽  
Elizabeth Hervey ◽  
G. R. Hervey
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Normal Weight ◽  
Oestrous Cycle ◽  
Zucker Rats ◽  
Central Regulation ◽  
Normal Pattern ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats

Congenitally obese Zucker rats showed greater food intake, less running in activity wheels and greater body weight and fat content than the normal phenotype. Their food intake, running and body weight did not change significantly with the phase of the oestrous cycle. Ovariectomy had no effect on these variables or on body composition. Oestradiol replacement had little effect. Zucker rats of normal weight, however, showed a normal pattern of responses to the oestrous cycle, ovariectomy and oestradiol administration. The central regulation of energy balance and body weight appear to be insensitive to oestrogens in the obese Zucker rat.

Intraventricular insulin reduces food intake and body weight of lean but not obese zucker rats

Appetite ◽  
1986 ◽  
Vol 7 (4) ◽  
pp. 381-386 ◽  
Author(s):  
H. Ikeda ◽  
D.B. West ◽  
J.J. Pustek ◽  
D.P. Figlewicz ◽  
M.R.C. Greenwood ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Zucker Rats ◽  
Obese Zucker Rats

987 des-acyl Ghrelin Suppresses Food Intake and Body Weight Gain in Adult Obese Zucker Rats

2008 ◽  
Vol 134 (4) ◽  
pp. A-148 ◽  
Author(s):  
Andreas Stengel ◽  
Anna-Sophia Wisser ◽  
Peter Kobelt ◽  
Miriam Goebel ◽  
Bertram Wiedenmann ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Acyl Ghrelin

Central melanocortin system modulates energy intake and expenditure of obese and lean Zucker rats

2001 ◽  
Vol 281 (2) ◽  
pp. R444-R451 ◽  
Author(s):  
Joyce J. Hwa ◽  
Lorraine Ghibaudi ◽  
Jun Gao ◽  
Eric M. Parker
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Receptor Agonist ◽  
Melanocortin Receptor ◽  
Zucker Rats ◽  
Light Cycle ◽  
Weight Regulation ◽  
Central Administration ◽  
Body Weight Regulation ◽  
Obese Zucker Rats

Melanocortins play a critical role in appetite and body weight regulation, because manipulations of this pathway can lead to the development of obesity in several animal models. The purpose of this study was to use a melanocortin receptor agonist and antagonist to evaluate the involvement of melanocortins in feeding, energy metabolism, and body weight regulation in lean and obese Zucker rats. Central administration of a melanocortin receptor antagonist (SHU9119) elevated food intake and body weight of lean Zucker rats but had little effect in obese Zucker rats. In contrast, the melanocortin receptor agonist MTII reduced food intake in both lean and obese rats but was more potent in the obese Zucker rats. These data indicate the existence of functional melanocortin receptors in both lean and obese Zucker rats but suggest that obese Zucker rats have reduced endogenous melanocortin tone. In addition to its effects on food intake, MTII infusion elevated oxygen consumption and decreased respiratory quotient dose dependently during the light cycle. Our data suggest that a melanocortin receptor agonist can induce weight loss by increasing energy expenditure and promoting body fat utilization in addition to its inhibitory effects on food intake in both obese and lean Zucker rats.

Effects of clenbuterol on insulin resistance in conscious obese Zucker rats

2001 ◽  
Vol 280 (4) ◽  
pp. E554-E561 ◽  
Author(s):  
Shujia J. Pan ◽  
Joe Hancock ◽  
Zhenping Ding ◽  
Donovan Fogt ◽  
Mancheong Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Chronic Administration ◽  
Abdominal Fat ◽  
Zucker Rats ◽  
Control Group ◽  
Obese Zucker Rats ◽  
Long Acting

The present study was conducted to determine the effect of chronic administration of the long-acting β2-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats ( fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin · kg−1 · min−1) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.

scholarly journals Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats

2012 ◽  
Vol 302 (1) ◽  
pp. R137-R142 ◽  
Author(s):  
Elizabeth M. Marchionne ◽  
Maggie K. Diamond-Stanic ◽  
Mujalin Prasonnarong ◽  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Renin Inhibition

We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker ( fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser473 phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the strategy of targeting the RAS to improve both blood pressure regulation and insulin action in conditions of insulin resistance.

scholarly journals Chronic Central Leptin Decreases Food Intake and Improves Glucose Tolerance in Diet-Induced Obese Mice Independent of Hypothalamic Malonyl CoA Levels and Skeletal Muscle Insulin Sensitivity

Endocrinology ◽  
2011 ◽  
Vol 152 (11) ◽  
pp. 4127-4137 ◽  
Author(s):  
Wendy Keung ◽  
Arivazhagan Palaniyappan ◽  
Gary D. Lopaschuk
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Tolerance Test ◽  
Acid Oxidation ◽  
Obese Mice ◽  
Malonyl Coa ◽  
Skeletal Muscle Insulin Sensitivity

Although acute leptin administration in the hypothalamus decreases food intake and increases peripheral energy metabolism, the peripheral actions of central chronic leptin administration are less understood. In this study, we investigated what effects chronic (7 d) intracerebroventricular (ICV) administration of leptin has on energy metabolism and insulin sensitivity in diet-induced obese mice. C57/BL mice were fed a low-fat diet (LFD; 10% total calories) or high-fat diet (HFD; 60% total calories) for 8 wk after which leptin was administered ICV for 7 consecutive days. Mice fed a HFD showed signs of insulin resistance, as evidenced by an impaired glucose tolerance test. Chronic leptin treatment resulted in a decrease in food intake and body weight and normalization of glucose clearance but no improvement in insulin sensitivity. Chronic ICV leptin increased hypothalamic signal transducer and activator of transcription-3 and AMP-activated protein kinase phosphorylation but did not change hypothalamic malonyl CoA levels in HFD fed and LFD-fed mice. In the gastrocnemius muscles, the levels of malonyl CoA in both leptin-treated groups were lower than their respective control groups, suggesting an increase in fatty acid oxidation. However, only in the muscles of ICV leptin-treated LFD mice was there a decrease in lipid metabolites including diacylglycerol, triacylglycerol, and ceramide. Our results suggest that chronic ICV leptin decreases food consumption and body weight via a mechanism different from acute ICV leptin administration. Although chronic ICV leptin treatment in HFD mice improves glucose tolerance, this occurs independent of changes in insulin sensitivity in the muscles of HFD mice.

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