Evaluation of in vivo insulin action and glucose metabolism in milk-fed rats

1992 ◽  
Vol 12 (4) ◽  
pp. 273-280 ◽  
Author(s):  
M. Kergoat ◽  
Ch. Gespach ◽  
G. Rosselin ◽  
B. Portha
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Female Rats ◽  
Whole Body ◽  
Utilization Rate ◽  
High Fat ◽  
Milk Feeding

Milk diet has long been recommended in the management of gastrointestinal pathologies. Since milk feeding represents a high fat-low carbohydrate diet and it is acknowledged that insulin resistance is one of the consequences of high fat feeding, it is important to know whether or not chronic milk feeding leads to an impairment of the insulin-mediated glucose metabolism. To examine this question, adult female rats were given raw cow's milk (50% of total calories as lipids) for 18 days. They were compared to rats raised in parallel and fed the standard laboratory diet (15% of total calories as lipids). At the end of the 18 day period, body weight, daily caloric intake, basal plasma glucose and insulin levels in the milk-fed rats were similar to those in the control rats. In vivo insulin action was assessed with the euglycemichyperinsulinemic clamp technique in anesthetized animals. These studies were coupled with the 2-deoxyglucose technique allowing a measurement of glucose utilization by individual tissues. In the milk fed rats: 1) the basal rate of endogenous glucose production was significantly (p<0.01) reduced (by 20%); 2) their hepatic glucose production was however normally suppressed by hyperinsulinemia; 3) their basal glucose utilization rate was significantly (p<0.01) reduced (by 20%); 4) their glucose utilization rate by the whole-body mass or by individual tissues was normally increased by hyperinsulinemia. These results indicate that insulin action in adult rats is not grossly altered after chronic milk-feeding, at least under the present experimental conditions.

scholarly journals Insulin action and glucose metabolism in sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 459-471 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Metabolic Clearance ◽  
Endogenous Glucose

1. The effect of an exogenous supply of glucose, provided by the digestion of maize starch in the small intestine, on endogenous glucose metabolism and insulin action was studied in sheep using the euglycaemic insulin clamp procedure.2. Insulin was infused intravenously at rates of 0.2, 0.5, 1.0 and 6.0 mU/min per kg live weight for four consecutive periods in each of four sheep fed on dried-grass and maize-based diets. Glucose was also infused intravenously at a variable rate, sufficient to maintain the plasma glucose concentration at basal levels. Whole-body rates of glucose metabolism were determined using a continuous infusion of [6-3H]glucose.3. From the resultinginsulin dose-response curves, it was observed that, when the sheep were fed on the dried-grass diet, the responsiveness of glucose metabolism to insulin was less than that reported for non-ruminants.4. When fed the maize-based diet, the glucose metabolic clearance rates (MCR) observed during insulin infusions were significantly greater (P < 0.05) than those observed for the dried-grass diet. However, after correcting for the non-insulin-mediated glucose disposal, differences between diets were not significant.5. The sensitivity of glucose utilization to insulin was not affected by diet. The plasma insulin concentrations causing half-maximal insulin-mediated glucose MCR were 103 (SE 21) and 85 (SE 11) mU/l for the dried-grass and maize-based diets respectively.6. The sensitivity of endogenous glucose production to insulin was also unaffected by diet. The plasma insulin concentrations resulting in the suppression of endogenous glucose production to half the basal level were 80 (SE 26) and 89 (SE 29) mU/l for the dried-grass and maize-based diets respectively.7. It is concluded that the observed increase in glucose utilization on the maize-based diet was due partly to a slight change in responsiveness to insulin and also partly to a change in the rate of non-insulin-mediated glucose disposal.

GLUT2 and hexokinase control proximodistal gradient of intestinal glucose metabolism in the newborn pig

1997 ◽  
Vol 272 (6) ◽  
pp. G1530-G1539 ◽  
Author(s):  
C. Cherbuy ◽  
B. Darcy-Vrillon ◽  
L. Posho ◽  
P. Vaugelade ◽  
M. T. Morel ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Specific Effect ◽  
Glucose Consumption ◽  
Utilization Rate ◽  
Glucose Turnover ◽  
Proximal Jejunum ◽  
A Site

We have reported previously that a high glycolytic capacity develops soon after birth in enterocytes isolated from suckling newborn pigs. In the present work, we investigated whether such metabolic changes could affect intestinal glucose utilization in vivo and examined possible variations in glucose metabolism along the small intestine. Glucose utilization by individual tissues was assessed using the 2-deoxyglucose technique. The overall glucose utilization rate was doubled in suckling vs. fasting 2-day-old pigs because of significantly higher rates in all tissues studied, except for the brain. In parallel, enterocytes were isolated from the proximal, medium, or distal jejunoileum of newborn vs. 2-day-old pigs and assessed for their capacity to utilize, transport, and phosphorylate glucose. Intestinal glucose consumption accounted for approximately 15% of glucose turnover rate in suckling vs. 8% in fasting pigs. Moreover, there was a proximal-to-distal gradient of glucose utilization in the intestinal mucosa of suckling pigs. Such a gradient was also evidenced on isolated enterocytes. The stimulation of both hexokinase activity (HK2 isoform) and basolateral glucose transporter (GLUT2), as observed in the proximal jejunum, could account for such a site-specific effect of suckling.

scholarly journals Peroxisome Proliferator-Activated Receptor (PPAR) Activation Induces Tissue-Specific Effects on Fatty Acid Uptake and Metabolism in Vivo—A Study Using the Novel PPARα/γ Agonist Tesaglitazar

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3158-3164 ◽  
Author(s):  
Bronwyn D. Hegarty ◽  
Stuart M. Furler ◽  
Nicholas D. Oakes ◽  
Edward W. Kraegen ◽  
Gregory J. Cooney
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
High Fat

Abstract Agonists of peroxisome proliferator-activated receptors (PPARs) have emerged as important pharmacological agents for improving insulin action. A major mechanism of action of PPAR agonists is thought to involve the alteration of the tissue distribution of nonesterified fatty acid (NEFA) uptake and utilization. To test this hypothesis directly, we examined the effect of the novel PPARα/γ agonist tesaglitazar on whole-body insulin sensitivity and NEFA clearance into epididymal white adipose tissue (WAT), red gastrocnemius muscle, and liver in rats with dietary-induced insulin resistance. Wistar rats were fed a high-fat diet (59% of calories as fat) for 3 wk with or without treatment with tesaglitazar (1 μmol·kg−1·d−1, 7 d). NEFA clearance was measured using the partially metabolizable NEFA tracer, 3H-R-bromopalmitate, administered under conditions of basal or elevated NEFA availability. Tesaglitazar improved the insulin sensitivity of high-fat-fed rats, indicated by an increase in the glucose infusion rate during hyperinsulinemic-euglycemic clamp (P &lt; 0.01). This improvement in insulin action was associated with decreased diglyceride (P &lt; 0.05) and long chain acyl coenzyme A (P &lt; 0.05) in skeletal muscle. NEFA clearance into WAT of high-fat-fed rats was increased 52% by tesaglitazar under basal conditions (P &lt; 0.001). In addition the PPARα/γ agonist moderately increased hepatic and muscle NEFA utilization and reduced hepatic triglyceride accumulation (P &lt; 0.05). This study shows that tesaglitazar is an effective insulin-sensitizing agent in a mild dietary model of insulin resistance. Furthermore, we provide the first direct in vivo evidence that an agonist of both PPARα and PPARγ increases the ability of WAT, liver, and skeletal muscle to use fatty acids in association with its beneficial effects on insulin action in this model.

Glucose utilization and insulin action in adult rats submitted to prolonged food restriction

1992 ◽  
Vol 263 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
F. Escriva ◽  
C. Rodriguez ◽  
J. Cacho ◽  
C. Alvarez ◽  
B. Portha ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Action ◽  
Food Restriction ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Turnover ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Adult Rats ◽  
Peripheral Tissues

Glucose tolerance and insulin effects on glucose production and utilization by various tissues were studied in 70-day-old anesthetized rats submitted to food restriction from the fetal stage. Basal and glucose-induced plasma insulin levels were reduced in food-restricted rats without alterations in glucose tolerance. Insulin action was quantified by using the euglycemic-hyperinsulinemic clamp technique. Glucose turnover rates were measured by using D-[6-3H]glucose. Exogenous insulin failed to decrease glucose production in food-restricted rats. Weight-related whole body glucose utilization was higher in restricted rats than in controls both in the basal (21.9 +/- 0.7 vs. 9.4 +/- 0.6 mg.min-1.kg-1) and hyperinsulinemic states (37.5 +/- 1.1 vs. 14.0 +/- 1.2 mg.min-1.kg-1). Local glucose utilization by peripheral tissues was estimated by a 2-deoxy-D-[1-3H]glucose technique. In both basal and hyperinsulinemic conditions glucose utilization was increased in various adipose and muscle tissues of the food-restricted rats as compared with the controls. Thus we conclude that food restriction leads to an increase in the insulin-mediated glucose uptake by various peripheral tissues and to insulin resistance in the liver.

scholarly journals Overexpression of manganese superoxide dismutase ameliorates high-fat diet-induced insulin resistance in rat skeletal muscle

2012 ◽  
Vol 303 (6) ◽  
pp. E798-E805 ◽  
Author(s):  
Michael J. Boden ◽  
Amanda E. Brandon ◽  
Jennifer D. Tid-Ang ◽  
Elaine Preston ◽  
Donna Wilks ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Insulin Action ◽  
Manganese Superoxide Dismutase ◽  
Whole Body ◽  
High Fat ◽  
Muscle Insulin Resistance ◽  
Manganese Superoxide

Elevated mitochondrial reactive oxygen species have been suggested to play a causative role in some forms of muscle insulin resistance. However, the extent of their involvement in the development of diet-induced insulin resistance remains unclear. To investigate, manganese superoxide dismutase (MnSOD), a key mitochondrial-specific enzyme with antioxidant modality, was overexpressed, and the effect on in vivo muscle insulin resistance induced by a high-fat (HF) diet in rats was evaluated. Male Wistar rats were maintained on chow or HF diet. After 3 wk, in vivo electroporation (IVE) of MnSOD expression and empty vectors was undertaken in right and left tibialis cranialis (TC) muscles, respectively. After one more week, insulin action was evaluated using hyperinsulinemic euglycemic clamp, and tissues were subsequently analyzed for antioxidant enzyme capacity and markers of oxidative stress. MnSOD mRNA was overexpressed 4.5-fold, and protein levels were increased by 70%, with protein detected primarily in the mitochondrial fraction of muscle fibers. This was associated with elevated MnSOD and glutathione peroxidase activity, indicating that the overexpressed MnSOD was functionally active. The HF diet significantly reduced whole body and TC muscle insulin action, whereas overexpression of MnSOD in HF diet animals ameliorated this reduction in TC muscle glucose uptake by 50% ( P < 0.05). Decreased protein carbonylation was seen in MnSOD overexpressing TC muscle in HF-treated animals (20% vs. contralateral control leg, P < 0.05), suggesting that this effect was mediated through an altered redox state. Thus interventions causing elevation of mitochondrial antioxidant activity may offer protection against diet-induced insulin resistance in skeletal muscle.

scholarly journals Sex-specific programming of adult insulin resistance in guinea pigs by variable perinatal growth induced by spontaneous variation in litter size

2019 ◽  
Vol 316 (4) ◽  
pp. R352-R361
Author(s):  
Dane M. Horton ◽  
David A. Saint ◽  
Kathryn L. Gatford ◽  
Karen L. Kind ◽  
Julie A. Owens
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Guinea Pigs ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Catch Up ◽  
Endogenous Glucose

Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in programming of insulin resistance later in life. Spontaneous IUGR in the guinea pig, due to natural variation in litter size, produces offspring with asymmetric IUGR and neonatal catch-up growth. We hypothesized that spontaneous IUGR and/or accelerated neonatal growth would impair insulin sensitivity in adult guinea pigs. Insulin sensitivity of glucose metabolism was determined by hyperinsulinemic-euglycemic clamp (HEC) in 38 (21 male, 17 female) young adult guinea pigs from litters of two-to-four pups. A subset (10 male, 8 female) were infused with d-[3-3H]glucose before and during the HEC to determine rates of basal and insulin-stimulated glucose utilization, storage, glycolysis, and endogenous glucose production. n males, the insulin sensitivity of whole body glucose uptake ( r = 0.657, P = 0.002) and glucose utilization ( r = 0.884, P = 0.004) correlated positively and independently with birth weight, but not with neonatal fractional growth rate (FGR10–28). In females, the insulin sensitivity of whole body and partitioned glucose metabolism was not related to birth weight, but that of endogenous glucose production correlated negatively and independently with FGR10–28 ( r = −0.815, P = 0.025). Thus, perinatal growth programs insulin sensitivity of glucose metabolism in the young adult guinea pig and in a sex-specific manner; impaired insulin sensitivity, including glucose utilization, occurs after IUGR in males and impaired hepatic insulin sensitivity after rapid neonatal growth in females.

Increased insulin action in rats with mild insulin deficiency induced by neonatal streptozotocin

1991 ◽  
Vol 260 (4) ◽  
pp. E561-E567 ◽  
Author(s):  
M. Kergoat ◽  
M. Guerre-Millo ◽  
M. Lauva ◽  
B. Portha
Keyword(s):  
Adipose Tissue ◽  
Insulin Action ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Control Group ◽  
Insulin Deficiency ◽  
Brown Adipose

The effect of chronic moderate insulin deficiency on in vivo insulin action was studied in young rats after neonatal (day of birth) streptozotocin (n0-STZ model) at a time (4 wk) when basal hyperglycemia is not yet established. The insulin action was quantified in vivo during insulin-glucose clamps performed on anesthetized rats while in the postabsorptive state; under basal or hyperinsulinemic conditions, total glucose production and utilization were assessed with a [3- 3H]-glucose perfusion, and local glucose utilization was estimated by measuring 2-deoxy-D-[1-3H]glucose 6-phosphate accumulation in various tissues. Compared with controls, the 4-wk-old n0-STZ rats were normoglycemic and hypoinsulinemic (P less than 0.05). The basal glucose production rate in the diabetics was significantly greater (P less than 0.05). During the clamp studies, suppression of endogenous glucose production by submaximal (1 nmol/l) or maximal (30 nmol/l) hyperinsulinemia was similar in both groups. Overall glucose utilization in the diabetics was significantly higher in the basal state and, after submaximal or maximal hyperinsulinemia, it remained significantly greater (P less than 0.001) than the corresponding utilization in the controls. This was correlated with an increased stimulation of glucose utilization in soleus muscle, diaphragm, white adipose tissue, and brown adipose tissue. In vitro studies using inguinal adipocytes showed that the glucose oxidative pathway retained normal sensitivity to insulin in the n0-STZ rats while the glucose conversion into lipids was significantly higher at sub-maximal insulin concentration compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute activation of central GLP-1 receptors enhances hepatic insulin action and insulin secretion in high-fat-fed, insulin resistant mice

2012 ◽  
Vol 302 (3) ◽  
pp. E334-E343 ◽  
Author(s):  
Melissa A. Burmeister ◽  
Tura Ferre ◽  
Jennifer E. Ayala ◽  
Emily M. King ◽  
Rochelle M. Holt ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Insulin Action ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
High Fat ◽  
Intravenous Glucose ◽  
Insulin Levels ◽  
Triglyceride Accumulation

Glucagon-like peptide-1 (GLP-1) receptor knockout (Glp1r−/−) mice exhibit impaired hepatic insulin action. High fat (HF)-fed Glp1r−/− mice exhibit improved, rather than the expected impaired, hepatic insulin action. This is due to decreased lipogenic gene expression and triglyceride accumulation. The present studies overcome these secondary adaptations by acutely modulating GLP-1R action in HF-fed wild-type mice. The central GLP-1R was targeted given its role as a regulator of hepatic insulin action. We hypothesized that acute inhibition of the central GLP-1R impairs hepatic insulin action beyond the effects of HF feeding. We further hypothesized that activation of the central GLP-1R improves hepatic insulin action in HF-fed mice. Insulin action was assessed in conscious, unrestrained mice using the hyperinsulinemic euglycemic clamp. Mice received intracerebroventricular (icv) infusions of artificial cerebrospinal fluid, GLP-1, or the GLP-1R antagonist exendin-9 (Ex-9) during the clamp. Intracerebroventricular Ex-9 impaired the suppression of hepatic glucose production by insulin, whereas icv GLP-1 improved it. Neither treatment affected tissue glucose uptake. Intracerebroventricular GLP-1 enhanced activation of hepatic Akt and suppressed hypothalamic AMP-activated protein kinase. Central GLP-1R activation resulted in lower hepatic triglyceride levels but did not affect muscle, white adipose tissue, or plasma triglyceride levels during hyperinsulinemia. In response to oral but not intravenous glucose challenges, activation of the central GLP-1R improved glucose tolerance. This was associated with higher insulin levels. Inhibition of the central GLP-1R had no effect on oral or intravenous glucose tolerance. These results show that inhibition of the central GLP-1R deteriorates hepatic insulin action in HF-fed mice but does not affect whole body glucose homeostasis. Contrasting this, activation of the central GLP-1R improves glucose homeostasis in HF-fed mice by increasing insulin levels and enhancing hepatic insulin action.

Ethanol attenuates endotoxin-enhanced glucose utilization

1990 ◽  
Vol 258 (4) ◽  
pp. R987-R993
Author(s):  
P. E. Molina ◽  
C. H. Lang ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Adipose Tissue ◽  
Glucose Utilization ◽  
Fiber Type ◽  
Glucose Production ◽  
Experimental Period ◽  
Whole Body ◽  
Glucose Metabolic Rate ◽  
Prior Administration ◽  
Increased Susceptibility

Ethanol (EtOH) is known to alter various aspects of cellular metabolism. Among these, the blunting of the increased rate of glucose production and utilization by the host after the administration of endotoxin may be an important factor in the increased susceptibility to infections. Therefore the present study was conducted to determine which tissues are responsible for the attenuation of the endotoxin-induced increase in whole body glucose utilization after acute EtOH administration. In vivo glucose metabolic rate (Rg) of different organs was investigated in conscious rats by the tracer 2-deoxy-D-glucose technique. Rats received a slow intravenous bolus injection of EtOH (275 mg/100 g body wt of a 20% wt/vol solution) followed by a continuous infusion (25 mg/100 g body wt) that was maintained throughout the experimental period. Thirty minutes after initiation of the EtOH treatment, Escherichia coli endotoxin (100 micrograms/100 g body wt) was administered intravenously. Time-matched control animals received an equal volume of saline. EtOH alone affected Rg only in gastrocnemius muscle (30% decrease) and adipose tissue (twofold increase). Endotoxin alone increased Rg in all tissues examined except in heart and brain. Prior administration of EtOH inhibited the endotoxin-induced increased Rg in skeletal muscle (regardless of fiber type), ileum, liver, adipose tissue, and kidney, blunted the increase in spleen and lung, and did not alter the increased Rg in skin. Brain showed a 20% decrease in Rg in response to EtOH and endotoxin administration. The EtOH-attenuated increase in glucose utilization in the macrophage-rich tissues of endotoxin-treated rats may be a reflection of an impaired capacity of these tissues to respond to infection.

Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet

2002 ◽  
Vol 282 (4) ◽  
pp. E834-E842 ◽  
Author(s):  
Rémy Burcelin ◽  
Valérie Crivelli ◽  
Anabela Dacosta ◽  
Alexandra Roy-Tirelli ◽  
Bernard Thorens
Keyword(s):  
Glucose Uptake ◽  
Glucose Utilization ◽  
Intermediate Phenotype ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
High Fat ◽  
Insulin Resistant ◽  
Glucose Clearance

C57BL/6J mice were fed a high-fat, carbohydrate-free diet (HFD) for 9 mo. Approximately 50% of the mice became obese and diabetic (ObD), ∼10% lean and diabetic (LD), ∼10% lean and nondiabetic (LnD), and ∼30% displayed intermediate phenotype. All of the HFD mice were insulin resistant. In the fasted state, whole body glucose clearance was reduced in ObD mice, unchanged in the LD mice, and increased in the LnD mice compared with the normal-chow mice. Because fasted ObD mice were hyperinsulinemic and the lean mice slightly insulinopenic, there was no correlation between insulin levels and increased glucose utilization. In vivo, tissue glucose uptake assessed by 2-[14C]deoxyglucose accumulation was reduced in most muscles in the ObD mice but increased in the LnD mice compared with the values of the control mice. In the LD mice, the glucose uptake rates were reduced in extensor digitorum longus (EDL) and total hindlimb but increased in soleus, diaphragm, and heart. When assessed in vitro, glucose utilization rates in the absence and presence of insulin were similar in diaphragm, soleus, and EDL muscles isolated from all groups of mice. Thus, in genetically homogenous mice, HFD feeding lead to different metabolic adaptations. Whereas all of the mice became insulin resistant, this was associated, in obese mice, with decreased glucose clearance and hyperinsulinemia and, in lean mice, with increased glucose clearance in the presence of mild insulinopenia. Therefore, increased glucose clearance in lean mice could not be explained by increased insulin level, indicating that other in vivo mechanisms are triggered to control muscle glucose utilization. These adaptive mechanisms could participate in the protection against development of obesity.

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