Increased insulin sensitivity and responsiveness during lactation in rats

1986 ◽  
Vol 251 (5) ◽  
pp. E537-E541 ◽  
Author(s):  
A. F. Burnol ◽  
A. Leturque ◽  
P. Ferre ◽  
J. Kande ◽  
J. Girard
Keyword(s):  
Insulin Sensitivity ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Utilization Rate ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Maximal Effect ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Peripheral Tissues

In 12-day lactating rats blood glucose and plasma insulin were decreased by, respectively, 20 and 35% when compared with nonlactating rats, despite a 25% increase of their glucose turnover rate. Then, by using the euglycemic hyperinsulinemic clamp technique, dose-response curves for the effects of insulin on glucose production and utilization in lactating and nonlactating rats were performed. Glucose production rate was totally suppressed at 250 microU/ml of insulin in lactating rats and for plasma insulin concentrations higher than 500 microU/ml in nonlactating rats. Plasma insulin level inducing half-maximal inhibition of glucose production was decreased by 60% during lactation. The maximal effect of insulin on glucose utilization rate and glucose metabolic clearance rate was, respectively, increased 1.5- and 2.4-fold during lactation and was obtained for plasma insulin concentrations lower in lactating than in nonlactating rats (250 vs. 500 microU/ml). Insulin concentrations inducing half-maximal stimulation of glucose utilization and glucose metabolic clearance were decreased by 50% during lactation. In conclusion, this study has shown that insulin sensitivity and responsiveness of liver and peripheral tissues are improved at peak lactation in the rat.

Effects of norepinephrine infusion on in vivo insulin sensitivity and responsiveness

1990 ◽  
Vol 259 (2) ◽  
pp. E210-E215 ◽  
Author(s):  
J. R. Lupien ◽  
M. F. Hirshman ◽  
E. S. Horton
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Adrenergic Blockade ◽  
Sprague Dawley ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Peripheral Tissues

The effect of a continuous infusion of norepinephrine (NE) on glucose disposal in vivo was examined in conscious restrained rats using the euglycemic-hyperinsulinemic clamp technique. NE, 1,000 micrograms.kg-1.day-1 (130 nmol.kg-1.h-1) or vehicle (CO) was infused for 10 days in adult male Sprague-Dawley rats using subcutaneously implanted osmotic minipumps. Body weight and food intake were similar in both groups of animals throughout the study. Fasting basal plasma glucose and insulin concentrations were similar in both groups. However, basal hepatic glucose production (HGP) was increased by NE treatment (9.03 +/- 0.63 vs. 13.20 +/- 1.15 mg.kg-1.min-1, P less than 0.05, CO vs. NE, respectively). Insulin infusions of 2, 6, and 200 mU.kg-1.min-1 suppressed HGP to the same degree in both groups. During 2, 6, and 200 mU.kg-1.h-1 insulin infusions the glucose disposal rate was 65, 60, and 13% greater in NE-treated animals than in controls. Acute beta-adrenergic blockade with propranolol infused at 405 nmol.kg-1.h-1 during the glucose clamps did not normalize glucose disposal. These results demonstrate that chronic NE infusion is associated with increased basal glucose turnover and increased insulin sensitivity of peripheral tissues.

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 Initial glucose kinetics and hormonal response to a gastric glucose load in unrestrained post-absorptive and starved rats

1990 ◽  
Vol 270 (2) ◽  
pp. 505-510 ◽  
Author(s):  
C Smadja ◽  
J Morin ◽  
P Ferré ◽  
J Girard
Keyword(s):  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Lactate Concentration ◽  
Glucose Production ◽  
Utilization Rate ◽  
Glucose Turnover ◽  
Glucose Load ◽  
Peripheral Tissues ◽  
Glucose Ingestion ◽  
Total Glucose

A gastric [U-14C]glucose load (4.8 mg/g body wt.) was delivered to unrestrained post-absorptive or 30 h-starved rats bearing peripheral and portal vein catheters and continuously perfused with [3-3H]glucose, in order to compare their metabolic and hormonal responses. In the basal state, portal and peripheral glycaemia were less in starved rats than in rats in the post-absorptive period (P less than 0.01), whereas blood lactate was similar. Portal insulinaemia (P less than 0.05) and protal glucagonaemia (P less than 0.005) were lower in starved rats, but insulin/glucagon ratio was higher in post-absorptive rats (P less than 0.005). The glucose turnover rate was decreased by starvation (P less than 0.005). After glucose ingestion, blood glucose was similar in post-absorptive and starved rats. A large portoperipheral gradient of lactate appeared in starved rats. Portal insulinaemia reached a peak at 9 min, and was respectively 454 +/- 68 and 740 +/- 65 mu-units/ml in starved and post-absorptive rats. Portal glucagonaemia remained stable, but was higher in post-absorptive rats (P less than 0.05). At 60 min after the gastric glucose load, 30% of the glucose was delivered at the periphery in both groups. The total glucose appearance rate was higher in starved rats (P less than 0.05), as was the glucose utilization rate (P less than 0.05), whereas the rate of appearance of exogenous glucose was similar. This was due to a non-suppressed hepatic glucose production in the starved rats, whereas it was totally suppressed in post-absorptive rats. At 1 h after the glucose load, the increase in both liver and muscle glycogen concentration was greater in starved rats. Thus short-term fasting induces an increased portal lactate concentration after a glucose load, and produces a state of liver insulin unresponsiveness for glucose production, whereas the sensitivity of peripheral tissues for glucose utilization is unchanged or even increased. This might allow preferential replenishment of the peripheral stores of glycogen.

Persistent glucose production and greater peripheral sensitivity to insulin in the neonate vs. the adult

1997 ◽  
Vol 272 (1) ◽  
pp. E86-E93 ◽  
Author(s):  
H. M. Farrag ◽  
L. M. Nawrath ◽  
J. E. Healey ◽  
E. J. Dorcus ◽  
R. E. Rapoza ◽  
...  
Keyword(s):  
Infusion Rate ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Metabolic Clearance ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Clinical Appearance ◽  
Stable Isotopic ◽  
Human Neonate ◽  
Resistance To Insulin ◽  
First Time

Insulin resistance has been reported to partially explain the clinical appearance of neonatal hyperglycemia. To determine the relative resistance to insulin of glucose production vs. glucose utilization, the euglycemic hyperinsulinemic clamp technique was employed for the first time in the human neonate and was combined with stable isotopic determination of glucose production and glucose utilization. The basal rates of glucose production and glucose utilization were determined, after which each neonate was clamped at his or her own euglycemic glucose concentration while receiving regular human insulin at one rate of 0.2, 0.5, 1.0, 2.0, or 4.0 mU. kg-1.min-1. Persistent glucose production (> or = 1 mg.kg-1.min-1) during the clamp was recorded for all groups. A significant increase in the glucose infusion rate (P < 0.001) and in percent glucose utilization (P < 0.01) occurred in the 2.0 and 4.0 mU.kg-1.min-1 insulin groups. Metabolic clearance rate of insulin was significantly greater in the neonate compared with the adult at the 2.0 mU.kg-1.min-1 insulin infusion rate (P = 0.036). Our results indicate that, in contrast to the adult, the neonate has persistent glucose production (P = 0.001) and greater peripheral sensitivity to insulin (P = 0.015).

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.

Insulin resistance during suckling period in rats

1987 ◽  
Vol 253 (2) ◽  
pp. E142-E148 ◽  
Author(s):  
T. Issad ◽  
C. Coupe ◽  
P. Ferre ◽  
J. Girard
Keyword(s):  
Insulin Resistance ◽  
Plasma Insulin ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Plasma Insulin Concentration ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Suckling Rats ◽  
High Carbohydrate ◽  
Low Fat Diet

Glucose metabolism was studied in 13- to 15-day-old suckling rats and 28- to 30-day-old rats weaned at 19 days on a high-carbohydrate, low-fat diet. The glucose turnover rate in the basal state was similar in suckling and weaned rats (14 mg X min-1 X kg-1). Glucose infusion (20 mg X min-1 X kg-1) produced a moderate hyperglycemia in weaned rats (150 mg/dl), whereas the suckling rats developed a high hyperglycemia (280 mg/dl), despite a large increase of plasma insulin concentration. The effect of insulin on glucose kinetics was then assessed by the euglycemic-hyperinsulinemic clamp technique. The plasma insulin levels reached were 736 +/- 87 microU/ml in the suckling and 444 +/- 34 microU/ml in the weaned rats, despite similar insulin infusion rates. Hepatic glucose production was suppressed by 90% in the weaned rats, whereas it remained at 40% of basal value in the suckling rats. The increase of glucose utilization above basal was fourfold higher in the weaned than in the suckling rats. Thus an insulin resistance state is present in the suckling rats and disappears after weaning onto a high-carbohydrate diet.

scholarly journals Development of insulin-sensitivity at weaning in the rat. Role of the nutritional transition

1988 ◽  
Vol 251 (3) ◽  
pp. 685-690 ◽  
Author(s):  
T Issad ◽  
C Coupé ◽  
M Pastor-Anglada ◽  
P Ferré ◽  
J Girard
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Clearance Rate ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Turnover Rates ◽  
Suckling Rats ◽  
Glucose Clearance

This study was undertaken to determine the factors involved in the development of insulin-sensitivity at weaning. Glucose kinetics were studied in suckling rats and in rats weaned on to a high-carbohydrate (HC) or a high-fat (HF) diet, in the basal state and during euglycaemic-hyperinsulinaemic-clamp studies. These studies were coupled with the 2-deoxyglucose technique, allowing a measure of glucose utilization by individual tissues. In the basal state, the glycaemia was higher in HF-weaned rats (124 +/- 4 mg/dl) than in suckling (109 +/- 1 mg/dl) and HC-weaned rats (101 +/- 3 mg/dl). Glucose turnover rates were similar in the three groups of animals (14 mg/min per kg). Nevertheless, basal metabolic glucose clearance rate was 20% lower in HF-weaned rats than in the other groups. During the euglycaemic-hyperinsulinaemic experiments, hepatic glucose production was suppressed by 90% in HC-weaned rats, whereas it remained at 40% of basal value in suckling and HF-weaned rats, indicating an insulin resistance of liver of these animals. Glucose clearance rate during the clamp was 18.3 +/- 0.9 ml/min per kg in suckling rats, whereas it was 35.3 +/- 1.2 ml/min per kg in HC-weaned rats and 27.8 +/- 1.1 ml/min per kg in HF-weaned rats, indicating an insulin resistance of glucose utilization in suckling, and to a lower extent, in HF-weaned rats. The deoxyglucose technique showed that peripheral insulin resistance was localized in muscles and white adipose tissue of suckling and HF-weaned rats. These results indicate that the switch from milk to a HC diet is an important determinant of the development of insulin-sensitivity at weaning in the rat.

Pregnancy-induced insulin resistance in the rat: assessment by glucose clamp technique

1984 ◽  
Vol 246 (1) ◽  
pp. E25-E31 ◽  
Author(s):  
A. Leturque ◽  
A. F. Burnol ◽  
P. Ferre ◽  
J. Girard
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Dose Response ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Pregnant Rats ◽  
Peripheral Tissues ◽  
Glucose Clamp Technique ◽  
Glucose Clearance

To quantify and characterize the insulin resistance during pregnancy in the rat, a euglycemic hyperinsulinemic clamp was set up. Dose-response curves for the effects of five concentrations of insulin on glucose production, glucose utilization, and glucose clearance were performed in age-matched virgin and 19-day-pregnant rats. Glucose production and glucose utilization were measured by using [3-3H]-glucose. Glucose production was totally suppressed at plasma insulin concentrations higher than 1,000 microU/ml in the two groups. Insulin concentration causing half-maximal suppression of glucose production was about 70 microU/ml in virgin rats and 250 microU/ml in pregnant rats. Maximal glucose utilization was obtained at plasma insulin concentrations of 2,000 microU/ml. In pregnant rats maximal increment in glucose utilization was significantly lower (P less than 0.01) than in virgin rats. Insulin concentrations causing half-maximal stimulation of glucose utilization were 200 microU/ml in virgin rats and 500 in pregnant rats. As blood glucose concentration in virgin and pregnant rats was clamped at, respectively, 0.97 +/- 0.03 and 0.73 +/- 0.03 mg/ml, glucose clearance rates were calculated because this parameter is minimally affected by the changes in blood glucose concentrations. A normal maximal increment in glucose clearance in response to insulin was restored in pregnant rats but the rightward shift of the dose-response curve was maintained. Plasma insulin concentrations necessary for half-maximal increment of glucose clearance in the two groups were similar to that observed when the results were expressed as glucose utilization. Thus, insulin resistance during late pregnancy in the rat is characterized by a decreased sensitivity of liver and peripheral tissues to insulin.

A simulation model for glucose kinetics and estimates of glucose utilization rate in type 1 diabetic patients

1995 ◽  
Vol 268 (4) ◽  
pp. E766-E774
Author(s):  
M. A. Boroujerdi ◽  
A. M. Umpleby ◽  
R. H. Jones ◽  
P. H. Sonksen
Keyword(s):  
Insulin Therapy ◽  
Plasma Glucose ◽  
Glucose Utilization ◽  
Model Simulation ◽  
Glucose Production ◽  
Glucose Transporters ◽  
High Plasma ◽  
Utilization Rate ◽  
Diabetic Patients ◽  
Metabolic Clearance

A glucose kinetic model is described that contains insulin-independent and insulin-dependent pathways of glucose uptake and includes a saturating flux term for glucose transport into the cells by the glucose transporters. The rate of glucose utilization was estimated in control subjects and diabetic patients by use of a bolus of [3-3H]glucose. Diabetic patients were studied after three regimens of insulin therapy: 1) after 24 h of insulin withdrawal, 2) after conventional insulin therapy, and 3) after an overnight insulin infusion such that plasma glucose was maintained between 4 and 6 mmol/l. In addition, the model was used to simulate published results from glucose clamp experiments with a range of glycemic levels and insulin concentrations. Estimates of glucose utilization flux in diabetic patients and model simulation suggest that high plasma glucose concentrations in uncontrolled diabetic patients can be attributed to a high glucose production rate by the liver associated with a reduction in glucose metabolic clearance rate due to relative saturation of the available pool of glucose transporters.

scholarly journals Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

2013 ◽  
Vol 305 (2) ◽  
pp. R110-R117 ◽  
Author(s):  
Jaymelynn K. Farney ◽  
Laman K. Mamedova ◽  
Johann F. Coetzee ◽  
Butch KuKanich ◽  
Lorraine M. Sordillo ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Physiological State ◽  
Plasma Glucose Concentration ◽  
Utilization Rate ◽  
Peripheral Tissues ◽  
Tnf Α ◽  
Anti Inflammatory

Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.

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