Gestational postprandial insulin sensitivity in the Sprague Dawley rat: the putative role of hepatic insulin sensitizing substance in glucose partitioning in pregnancy

2020 ◽  
Vol 98 (8) ◽  
pp. 541-547
Author(s):  
Nicole E.J. Lovat ◽  
Dallas J. Legare ◽  
Randall S. Gieni ◽  
W. Wayne Lautt
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Plasma Insulin ◽  
Sprague Dawley ◽  
Fed State ◽  
Triglyceride Concentration ◽  
Insulin Dependent ◽  
Postprandial Insulin ◽  
Glucose Partitioning ◽  
In Pregnancy

Pregnancy requires adaptation of maternal insulin sensitivity. In the fed state, a pulse of insulin stimulates glucose uptake and nutrient energy storage via insulin-dependent as well as hepatic insulin sensitizing substance (HISS)-dependent action. HISS is released by the liver in the fed state in the presence of signals integrated through the liver and a pulse of insulin. HISS promotes glucose storage as glycogen in heart, kidney, and skeletal muscle but not in gut, liver, or adipose tissue. HISS is also responsible for the vasodilatory action previously attributed to insulin. The rapid insulin sensitivity test (RIST), a dynamic euglycemic clamp, can quantitate both HISS-dependent and insulin-dependent glucose uptake. The RIST was used to characterize postprandial insulin sensitivity in the Sprague Dawley rat and the changes in the partitioning of nutrient energy throughout gestation. Early pregnancy demonstrated increased insulin sensitivity attributable to HISS-dependent glucose uptake with unchanged insulin-dependent glucose uptake, preserved plasma insulin concentration, and reduced plasma triglyceride concentration compared to the virgin. In late pregnancy, there was reduced HISS-dependent and insulin-dependent glucose uptake accompanied by increased plasma insulin and triglyceride concentration compared to the virgin. These results suggest an important role for HISS in glucose partitioning in pregnancy.

scholarly journals An animal model of gestational obesity and prediabetes: HISS-dependent insulin resistance induced by a high sucrose diet in Sprague Dawley rats.

2020 ◽  
Author(s):  
Nicole Eleanore Jacqueline Lovat ◽  
Dallas J. Legare ◽  
W. Wayne Lautt
Keyword(s):  
Insulin Resistance ◽  
Animal Model ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Complete Recovery ◽  
Partial Recovery ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Nutrient Partitioning ◽  
Insulin Dependent

This study developed an animal model of gestational obesity and prediabetes in Sprague Dawley rats using 35% sucrose supplementation (SS). Postprandially, insulin stimulates glucose uptake and nutrient partitioning via insulin-dependent as well as Hepatic Insulin Sensitizing Substance (HISS)-dependent action. HISS is glycogenic in heart, kidney, and skeletal muscle (contrasting insulin’s lipogenic actions in liver and adipose tissue) and is responsible for the vasodilatory action of insulin. Post-prandial insulin sensitivity was quantified using the Rapid Insulin Sensitivity Test (RIST). 15-day gestation and virgin animals received SS for 8-weeks (with a 2-week recovery), 10-weeks or 22-weeks. SS in pregnant and virgin rats eliminated HISS-dependent glucose uptake, resulting in compensatory hyperinsulinemia and resultant hypertriglyceridemia and obesity. In groups with SS for 8-weeks followed by a 2-week recovery, there was spontaneous partial recovery of HISS-dependent glucose uptake in virgins and complete recovery in pregnancy. 10-week SS resulted in complete absence of HISS-dependent glucose uptake and produced a model of gestational obesity and prediabetes. 22-week SS did not produce hyperglycemia or worsen hyperinsulinemia but did increase hypertriglyceridemia above 10-week SS. This substantiates the use of 10-week SS as a model of gestational obesity/prediabetes, allowing further studies into treatments of gestational obesity and insulin resistance.

scholarly journals The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hui Wu ◽  
Chunhua Sui ◽  
Hui Xu ◽  
Fangzhen Xia ◽  
Hualing Zhai ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Production ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Peripheral Tissues ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Glucagon Like Peptide 1

Objective. Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues.Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose.Results. In the diabetic rats, exenatide reduced the basalRaof glucose (P<0.01) and glycerol (P<0.01) and GNG (P<0.001). During the clamp,Raof glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P<0.01) during the clamp. In the nondiabetic rats, exenatide had no effect.Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

scholarly journals Acute effects of meal fatty acid composition on insulin sensitivity in healthy post-menopausal women

2002 ◽  
Vol 88 (6) ◽  
pp. 635-640 ◽  
Author(s):  
M. D. Robertson ◽  
K. G. Jackson ◽  
B. A. Fielding ◽  
C. M. Williams ◽  
K. N. Frayn
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Acid Composition ◽  
Plasma Insulin ◽  
High Fat ◽  
Menopausal Women ◽  
Post Menopausal ◽  
Postprandial Insulin

Postprandial plasma insulin concentrations after a single high-fat meal may be modified by the presence of specific fatty acids although the effects of sequential meal ingestion are unknown. The aim of the present study was to examine the effects of altering the fatty acid composition in a single mixed fat–carbohydrate meal on glucose metabolism and insulin sensitivity of a second meal eaten 5 h later. Insulin sensitivity was assessed using a minimal model approach. Ten healthy post-menopausal women underwent four two-meal studies in random order. A high-fat breakfast (40 g fat) where the fatty acid composition was predominantly saturated fatty acids (SFA),n-6 polyunsaturated fatty acids (PUFA), long-chainn-3 PUFA or monounsaturated fatty acids (MUFA) was followed 5 h later by a low-fat, high-carbohydrate lunch (5·7 g fat), which was identical in all four studies. The plasma insulin response was significantly higher following the SFA meal than the other meals after both breakfast and lunch (P<0·006) although there was no effect of breakfast fatty acid composition on plasma glucose concentrations. Postprandial insulin sensitivity (SI(Oral)) was assessed for 180 min after each meal. SI(Oral)was significantly lower after lunch than after breakfast for all four test meals (P=0·019) following the same rank order (SFA <n-6 PUFA <n-3 PUFA < MUFA) for each meal. The present study demonstrates that a single meal rich in SFA reduces postprandial insulin sensitivity with ‘carry-over’ effects for the next meal.

Accretion of visceral fat and hepatic insulin resistance in pregnant rats

2008 ◽  
Vol 294 (2) ◽  
pp. E451-E455 ◽  
Author(s):  
Francine H. Einstein ◽  
Sigal Fishman ◽  
Radhika H. Muzumdar ◽  
Xiao Man Yang ◽  
Gil Atzmon ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Visceral Fat ◽  
Hepatic Glucose Production ◽  
Late Gestation ◽  
Hepatic Insulin Resistance ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Hepatic Insulin Sensitivity ◽  
In Pregnancy

Insulin resistance (IR) is a hallmark of pregnancy. Because increased visceral fat (VF) is associated with IR in nonpregnant states, we reasoned that fat accretion might be important in the development of IR during pregnancy. To determine whether VF depots increase in pregnancy and whether VF contributes to IR, we studied three groups of 6-mo-old female Sprague-Dawley rats: 1) nonpregnant sham-operated rats (Nonpreg; n = 6), 2) pregnant sham-operated rats (Preg; n = 6), and 3) pregnant rats in which VF was surgically removed 1 mo before mating (PVF−; n = 6). VF doubled by day 19 of pregnancy (Nonpreg 5.1 ± 0.3, Preg 10.0 ± 1.0 g, P < 0.01), and PVF− had similar amounts of VF compared with Nonpreg (PVF− 4.6 ± 0.8 g). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp in late gestation in chronically catheterized unstressed rats. Glucose IR (mg·kg−1·min−1) was highest in Nonpreg (19.4 ± 2.0), lowest in Preg (11.1 ± 1.4), and intermediate in PVF− (14.7 ± 0.6; P < 0.001 between all groups). During the clamp, Nonpreg had greater hepatic insulin sensitivity than Preg [hepatic glucose production (HGP): Nonpreg 4.5 ± 1.3, Preg 9.3 ± 0.5 mg·kg−1·min−1; P < 0.001]. With decreased VF, hepatic insulin sensitivity was similar to nonpregnant levels in PVF− (HGP 4.9 ± 0.8 mg·kg−1·min−1). Both pregnant groups had lower peripheral glucose uptake compared with Nonpreg. In parallel with hepatic insulin sensitivity, hepatic triglyceride content was increased in pregnancy (Nonpreg 1.9 ± 0.4 vs. Preg 3.2 ± 0.3 mg/g) and decreased with removal of VF (PVF− 1.3 ± 0.4 mg/g; P < 0.05). Accretion of visceral fat is an important component in the development of hepatic IR in pregnancy, and accumulation of hepatic triglycerides is a mechanism by which visceral fat may modulate insulin action in pregnancy.

Increased skeletal muscle capillarization enhances insulin sensitivity

2014 ◽  
Vol 307 (12) ◽  
pp. E1105-E1116 ◽  
Author(s):  
Thorbjorn Akerstrom ◽  
Lasse Laub ◽  
Kenneth Vedel ◽  
Christian Lehn Brand ◽  
Bente Klarlund Pedersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Blood Stream ◽  
Whole Body ◽  
Glucose Disposal ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats ( n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[3H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[3H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes.

scholarly journals Insulin Clearance in Obesity and Type 2 Diabetes

2022 ◽  
Vol 23 (2) ◽  
pp. 596
Author(s):  
Han-Chow E. Koh ◽  
Chao Cao ◽  
Bettina Mittendorfer
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Plasma Insulin ◽  
Insulin Clearance ◽  
Plasma Insulin Concentration ◽  
Compensatory Response ◽  
Excess Adiposity ◽  
Insulin Secretion Rate ◽  
Postprandial Insulin

Plasma insulin clearance is an important determinant of plasma insulin concentration. In this review, we provide an overview of the factors that regulate insulin removal from plasma and discuss the interrelationships among plasma insulin clearance, excess adiposity, insulin sensitivity, and type 2 diabetes (T2D). We conclude with the perspective that the commonly observed lower insulin clearance rate in people with obesity, compared with lean people, is not a compensatory response to insulin resistance but occurs because insulin sensitivity and insulin clearance are mechanistically, directly linked. Furthermore, insulin clearance decreases postprandially because of the marked increase in insulin delivery to tissues that clear insulin. The commonly observed high postprandial insulin clearance in people with obesity and T2D likely results from the relatively low insulin secretion rate, not an impaired adaptation of tissues that clear insulin.

Abstract 1651: Exercise Improves Aging-associated Myocardial Insulin Resistance by Enhancing Mitochondrial Function in an eNOS Dependent Mechanism

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Qiu X Li ◽  
Quan J Zhang ◽  
Hai F Zhang ◽  
Kun R Zhang ◽  
Jia Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Mitochondrial Function ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Enos Expression ◽  
Adult Heart ◽  
Aging Heart ◽  
Myocardial Insulin Resistance

Objective . This study sought to determine whether exercise reduces aging-associated myocardial insulin resistance, with a specific focus on the role of eNOS and its relation to mitochondria. Methods . Aging male Sprague-Dawley rats (24 months) were subjected to swim training (60 min/d, 5 d/wk, 9 wk) or assigned as sedentary control. The myocardial contraction, myocardial glucose uptake, mitochondrial function, and eNOS signaling were determined. Results. Aging rats had myocardial insulin resistance as shown by decreased insulin-induced glucose uptake (0.22±0.05 μmol/min/g in aging heart vs.1.29 ± 0.13 μmol/min/g in adult heart, n=8, P <0.01) and attenuated insulin’s positive inotropic role as evidenced by reduced left ventricular developed pressure (90±12 mmHg in aging heart vs. 155±14 mmHg in adult heart, P <0.01). Mitochondrial function was decreased in aging hearts as manifested by the attenuated maximum O 2 consumption by FCCP (1.85±0.39 μmol/min/g in aging hearts vs. 3.72±0.40 μmol/min/g in adult hearts, P <0.01). This was accompanied with the reduced insulin-induced O 2 consumption (1.37±0.31 μmol/min/g in aging heart vs. 2.35±0.31 μmol/min/g in adult heart, P <0.01). In addition, eNOS expression and its phosphorylation by insulin were reduced by 1.2- and 2.3-fold in aging heart, respectively ( P <0.01). Swim training upregulated eNOS expression by 72% ( P <0.01), facilitated eNOS phosphorylation by insulin ( P <0.01), and improved myocardial insulin sensitivity as shown by enhanced glucose uptake by insulin ( P <0.01). Moreover, mitochondrial function was facilitated as manifested by the enhanced O 2 consumption by insulin ( P <0.05), and maximum O 2 consumption ( P <0.01) following swim training. Pretreatment with Cavtratin, an eNOS inhibitor, abolished exercise-improved mitochondrial response to insulin, blocked exercise-improved myocardial insulin sensitivity and the positive inotropic response to insulin in aging heart. Conclusion . These results demonstrate that impaired eNOS signaling and subsequent mitochondrial depression is a major mechanism contributes to aging-associated myocardial insulin resistance, and that exercise improves insulin sensitivity by restoring eNOS signaling and enhancing mitochondrial function.

Dietary fat modifies exercise-dependent glucose transport in skeletal muscle

1996 ◽  
Vol 80 (4) ◽  
pp. 1219-1224 ◽  
Author(s):  
S. Liu ◽  
V. E. Baracos ◽  
H. A. Quinney ◽  
M. T. Clandinin
Keyword(s):  
Glucose Uptake ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Acute Exercise ◽  
Sprague Dawley ◽  
High Fat ◽  
Lowered Sensitivity ◽  
Insulin Dependent ◽  
Fat Diets ◽  
20 Nm

Exercise stimulates muscle glucose uptake both directly and by increasing the sensitivity of this process to insulin. This study was designed to investigate whether the level of dietary fat would interact with the action of acute exercise in the presence or absence of insulin. Weanling female Sprague-Dawley rats were fed two levels of dietary fat (5 vs. 20%; wt/wt) for 6 wk. Rats then remained sedentary or were exercised by a single bout of swimming for a total of 2 h with 5-min rest intervals each 0.5 h. Basal (insulin-independent) and insulin-stimulated glucose uptake rates were determined in isolated epitrochlearis muscles by using 3-O-[methyl-3H]methyl-D-glucose. Muscles of sedentary rats fed a high-fat diet showed decreased glucose uptake overall because of a marked decrease in insulin-stimulated uptake. Muscles of rats fed a high-fat diet also showed considerable impairment of insulin-dependent glucose uptake measured both immediately and 3.5 h after exercise. Glucose uptake was suppressed by 64% at half-maximal concentrations of insulin (0.8 nM) and by 34% at maximally stimulating (20 nM) insulin levels. This lowered sensitivity and response to insulin were not altered by acute exercise. Glucose uptake in response to acute exercise (insulin independent) was quantitatively similar in rats fed high- and low-fat diets; rats on high-fat diet, however, showed higher insulin-independent glucose uptake at 3.5 h after exercise.

Effects of exercise intensity on insulin sensitivity in women with non-insulin-dependent diabetes mellitus

1995 ◽  
Vol 78 (1) ◽  
pp. 300-306 ◽  
Author(s):  
B. Braun ◽  
M. B. Zimmermann ◽  
N. Kretchmer
Keyword(s):  
Diabetes Mellitus ◽  
Steady State ◽  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Insulin Dependent Diabetes Mellitus ◽  
Glucose Disposal ◽  
Dependent Diabetes Mellitus ◽  
O2 Consumption ◽  
Insulin Dependent

Exercise enhances insulin sensitivity in people with non-insulin-dependent diabetes mellitus (NIDDM), but the intensity of exercise necessary to optimize the effect is unknown. Eight women with NIDDM were studied on a metabolic ward in each of three conditions: 1) low-intensity exercise (LO) that consisted of treadmill walking at 50% of maximal O2 consumption on days 1 and 2, 2) high-intensity exercise (HI) that consisted of walking at 75% of maximal O2 consumption, and 3) no exercise (NX). The duration of exercise was adjusted so that energy expenditure was equal in both exercise conditions. On day 3, glucose, [6,6–2H]glucose, and insulin were infused at fixed rates for 3 h. Insulin sensitivity was determined both by steady-state plasma glucose concentration and rate of glucose disposal per unit plasma insulin. Steady-state plasma glucose concentration and rate of glucose disposal per unit plasma insulin were almost identical after LO or HI; values were significantly greater than after NX. Plasma glucose response to a test meal was the same among the three conditions, but plasma insulin response was lower for HI and LO compared with NX. We conclude that under these conditions LO is as effective as HI in enhancing insulin sensitivity in people with NIDDM.

scholarly journals During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization

2019 ◽  
Vol 39 (20) ◽  
Author(s):  
Jong In Kim ◽  
Jeu Park ◽  
Yul Ji ◽  
Kyuri Jo ◽  
Sang Mun Han ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Lipid Droplet ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Filamentous Actin ◽  
Cytoskeleton Reorganization ◽  
Beige Adipocytes ◽  
Actin Structure ◽  
Insulin Dependent

ABSTRACT Adipocytes have unique morphological traits in insulin sensitivity control. However, how the appearance of adipocytes can determine insulin sensitivity has not been understood. Here, we demonstrate that actin cytoskeleton reorganization upon lipid droplet (LD) configurations in adipocytes plays important roles in insulin-dependent glucose uptake by regulating GLUT4 trafficking. Compared to white adipocytes, brown/beige adipocytes with multilocular LDs exhibited well-developed filamentous actin (F-actin) structure and potentiated GLUT4 translocation to the plasma membrane in the presence of insulin. In contrast, LD enlargement and unilocularization in adipocytes downregulated cortical F-actin formation, eventually leading to decreased F-actin-to-globular actin (G-actin) ratio and suppression of insulin-dependent GLUT4 trafficking. Pharmacological inhibition of actin polymerization accompanied with impaired F/G-actin dynamics reduced glucose uptake in adipose tissue and conferred systemic insulin resistance in mice. Thus, our study reveals that adipocyte remodeling with different LD configurations could be an important factor to determine insulin sensitivity by modulating F/G-actin dynamics.

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