Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantification in vivo of the effects of insulin on glucose utilization in individual tissues of warm- and cold-acclimated rats.

ABSTRACT: Cold-acclimation of rats (3 weeks, 4 degrees C) had no effect on basal rates of glucose production or utilization. Under euglycaemic-clamp conditions, in which the circulating insulin concentration was increased by approx. 50 microunits/ml, cold-acclimated rats showed a greater increase in glucose utilization and a greater suppression of endogenous glucose production. Tissue sites of glucose utilization were investigated by using a tracer dose of 2-deoxy-D-[14C]glucose and a glucose metabolic index determined for each tissue. In 5 h-starved warm-acclimated rats, heart had the highest glucose metabolic index. This was increased further by both cold-acclimation and insulin treatment. The glucose metabolic index of skeletal muscle was 3.5-14-fold lower than that of heart, but, as a result of the large muscle mass, skeletal muscle made the largest contribution to whole-body glucose utilization. White and brown adipose tissue had low glucose metabolic indices in warm-acclimated rats under basal conditions, and the indices were not increased by the insulin treatment. However, cold-acclimation produced a significant increase in the glucose metabolic index of brown adipose tissue, but not of white adipose tissue. In contrast with the warm-acclimated rats, insulin treatment of cold-acclimated rats resulted in a marked increase in the glucose metabolic index of brown adipose tissue. The results provide evidence that cold-acclimation produces a selective alteration in the insulin-sensitivity of brown adipose tissue.

SUBMITTER: Smith SA

PROVIDER: S-EPMC1147058 | biostudies-other | 1986 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

FoxO1 suppresses Fgf21 during hepatic insulin resistance to impair peripheral glucose utilization and acute cold tolerance.

Project description:Fgf21 (fibroblast growth factor 21) is a regulatory hepatokine that, in pharmacologic form, powerfully promotes weight loss and glucose homeostasis. Although "Fgf21 resistance" is inferred from higher plasma Fgf21 levels in insulin-resistant mice and humans, diminished Fgf21 function is understood primarily via Fgf21 knockout mice. By contrast, we show that modestly reduced Fgf21-owing to cell-autonomous suppression by hepatic FoxO1-contributes to dysregulated metabolism in LDKO mice (Irs1L/L⋅Irs2L/L⋅CreAlb), a model of severe hepatic insulin resistance caused by deletion of hepatic Irs1 (insulin receptor substrate 1) and Irs2. Knockout of hepatic Foxo1 in LDKO mice or direct restoration of Fgf21 by adenoviral infection restored glucose utilization by BAT (brown adipose tissue) and skeletal muscle, normalized thermogenic gene expression in LDKO BAT, and corrected acute cold intolerance of LDKO mice. These studies highlight the Fgf21-dependent plasticity and importance of BAT function to metabolic health during hepatic insulin resistance.

| S-EPMC8529953 | biostudies-literature

The Effect of Recovery Warm-up Time Following Cold Storage on the Dynamic Glucose-stimulated Insulin Secretion of Isolated Human Islets.

Project description:Standardized islet characterization assays that can provide results in a timely manner are essential for successful islet cell transplantation. A critical component of islet cell quality is β-cell function, and perifusion-based assessments of dynamic glucose-stimulated insulin secretion (GSIS) are the most informative method to assess this, as they provide the most complex in vitro evaluation of GSIS. However, protocols used vary considerably among centers and investigators as they often use different low- and high-glucose concentrations, exposure-times, flow-rates, oxygen concentrations, islet numbers, analytical methods, measurement units, and instruments, which result in different readouts and make comparisons across platforms difficult. Additionally, the conditions of islet storage and shipment prior to assessment may also affect islet function. Establishing improved standardized protocols for perifusion GSIS assays should be an integral part of the ongoing effort to increase the rigor of human islet studies. Here, we performed detailed evaluation of GSIS of human islets using a fully automated multichannel perifusion instrument following various warm-up recovery times after cold storage that corresponds to current shipping conditions (8°C). We found that recovery times shorter than 18 h (overnight) resulted in impaired insulin secretion. While the effects were relatively moderate on second-phase insulin secretion, first-phase peaks were restored only following 18-h incubation. Hence, the biphasic profile of dynamic GSIS was considerably affected when islets were not allowed to recover for a sufficient time after being maintained in cold. Accordingly, while cold storage might improve islet cell survival during shipment and prolong the length of culture, functional assessments should be performed only after allowing for at least overnight recovery at physiological temperatures.

| S-EPMC7444215 | biostudies-literature

ATPase-inhibitor proteins of brown-adipose-tissue mitochondria from warm- and cold-acclimated rats.

Project description:1. A group of male Sprague-Dawley rats (5-6 weeks old) was cold-acclimated at 4 degrees C for 4 weeks. Warm-acclimated controls remained at 24 degrees C. Total protein content of brown adipose tissue (BAT) increased more than 3-fold and total uncoupling protein (UCP) content increased more than 6-fold upon cold-acclimation. The concentration of UCP in isolated BAT mitochondria almost doubled. 2. Specific ATPase activity of the non-thermogenic BAT mitochondria (from warm-acclimated controls) was low and increased about 6-fold on addition of 1 microM-Ca2+, which raised free Ca2+ levels (measured by Fura-2) in the incubation media from 1.32 +/- 0.28 microM (mean +/- S.E.M.) to 2.29 +/- 0.39 microM [at which the Ca(2+)-binding ATPase-inhibitor protein (CaBI) is inactivated]. Correspondingly, the specific ATP synthetase activity of the non-thermogenic BAT mitochondria was high and was decreased by 74% by addition of 1 microM-Ca2+. 3. In contrast, specific ATPase activity of thermogenic BAT mitochondria (from cold-acclimated rats) was 5 times that of the control group, and addition of Ca2+ had only a small stimulatory response. Correspondingly, the specific ATP synthetase activity of the thermogenic BAT mitochondria was low, and the decrease by Ca2+ was small, albeit significant. 4. Extracts of BAT mitochondria from both groups of animals contained significant amounts of the ATPase-inhibitor protein of Pullman and Monroy (PMI) as well as of CaBI, as shown by gel electrophoresis. Kinetic studies of inhibition of mitochondrial ATPase activity showed that PMI activity was unaltered in extracts from the thermogenic BAT mitochondria, whereas CaBI activity was slightly but significantly increased. 5. The presence of active ATPase-inhibitor proteins in BAT mitochondria was shown for the first time. We conclude that uncoupling of oxidative phosphorylation occurs in thermogenic BAT mitochondria, even in the presence of the ATPase-inhibitor proteins.

| S-EPMC1133137 | biostudies-other

Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues.

Project description:Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake.

| S-EPMC4872141 | biostudies-literature

A warm jet in a cold ocean.

Project description:Unprecedented quantities of heat are entering the Pacific sector of the Arctic Ocean through Bering Strait, particularly during summer months. Though some heat is lost to the atmosphere during autumn cooling, a significant fraction of the incoming warm, salty water subducts (dives beneath) below a cooler fresher layer of near-surface water, subsequently extending hundreds of kilometers into the Beaufort Gyre. Upward turbulent mixing of these sub-surface pockets of heat is likely accelerating sea ice melt in the region. This Pacific-origin water brings both heat and unique biogeochemical properties, contributing to a changing Arctic ecosystem. However, our ability to understand or forecast the role of this incoming water mass has been hampered by lack of understanding of the physical processes controlling subduction and evolution of this this warm water. Crucially, the processes seen here occur at small horizontal scales not resolved by regional forecast models or climate simulations; new parameterizations must be developed that accurately represent the physics. Here we present novel high resolution observations showing the detailed process of subduction and initial evolution of warm Pacific-origin water in the southern Beaufort Gyre.

| S-EPMC8065036 | biostudies-literature

Exogenous thyroxine improves glucose intolerance in insulin-resistant rats.

Project description:Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T4) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T4 (8.0 µg/100 g BM/day × 5 weeks). T4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T4-treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (Mct10), deiodinase type 2 (Di2), sirtuin 1 (Sirt1) and uncoupling protein 2 (Ucp2) by 1.8-, 2.2-, 2.7- and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T4 treatment increased the influx of T4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis.

| S-EPMC5419047 | biostudies-literature

Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle.

Project description:Skeletal muscle is the principal tissue responsible for insulin-stimulated glucose disposal and is a major site of peripheral insulin resistance. Urocortin 2 (Ucn 2), a member of the corticotropin-releasing factor (CRF) family, and its cognate type 2 CRF receptor (CRFR2) are highly expressed in skeletal muscle. To determine the physiological role of Ucn 2, we generated mice that are deficient in this peptide. Using glucose-tolerance tests (GTTs), insulin-tolerance tests (ITTs), and hyperinsulinemic euglycemic glucose clamp studies, we demonstrated that mice lacking Ucn 2 exhibited increased insulin sensitivity and were protected against fat-induced insulin resistance. Administration of synthetic Ucn 2 to mutant mice before the GTTs and ITTs restored blood glucose to WT levels. Administration of a CRFR2 selective antagonist to WT mice resulted in a GTT profile that mirrored that of Ucn 2-null mice. Body composition measurements of Ucn 2-null mice on a high-fat diet demonstrated decreases in fat and increases in lean tissue compared with WT mice. We propose that null mutant mice display increased glucose uptake in skeletal muscle through the removal of Ucn 2-mediated inhibition of insulin signaling. In keeping with these data, Ucn 2 inhibited insulin-induced Akt and ERK1/2 phosphorylation in cultured skeletal muscle cells and C2C12 myotubes. These data are consistent with the hypothesis that Ucn 2 functions as a local negative regulator of glucose uptake in skeletal muscle and encourage exploration of the possibility that suppression of the Ucn 2/CRFR2 pathway may provide benefits in insulin-resistant states such as type 2 diabetes.

| S-EPMC1637624 | biostudies-literature

FoxO1 integrates direct and indirect effects of insulin on hepatic glucose production and glucose utilization.

Project description:FoxO proteins are major targets of insulin action. To better define the role of FoxO1 in mediating insulin effects in the liver, we generated liver-specific insulin receptor knockout (LIRKO) and IR/FoxO1 double knockout (LIRFKO) mice. Here we show that LIRKO mice are severely insulin resistant based on glucose, insulin and C-peptide levels, and glucose and insulin tolerance tests, and genetic deletion of hepatic FoxO1 reverses these effects. (13)C-glucose and insulin clamp studies indicate that regulation of both hepatic glucose production (HGP) and glucose utilization is impaired in LIRKO mice, and these defects are also restored in LIRFKO mice corresponding to changes in gene expression. We conclude that (1) inhibition of FoxO1 is critical for both direct (hepatic) and indirect effects of insulin on HGP and utilization, and (2) extrahepatic effects of insulin are sufficient to maintain normal whole-body and hepatic glucose metabolism when liver FoxO1 activity is disrupted.

| S-EPMC4755301 | biostudies-literature

In vivo quantification of spatially varying mechanical properties in developing tissues.

Project description:The mechanical properties of the cellular microenvironment and their spatiotemporal variations are thought to play a central role in sculpting embryonic tissues, maintaining organ architecture and controlling cell behavior, including cell differentiation. However, no direct in vivo and in situ measurement of mechanical properties within developing 3D tissues and organs has yet been performed. Here we introduce a technique that employs biocompatible, magnetically responsive ferrofluid microdroplets as local mechanical actuators and allows quantitative spatiotemporal measurements of mechanical properties in vivo. Using this technique, we show that vertebrate body elongation entails spatially varying tissue mechanics along the anteroposterior axis. Specifically, we find that the zebrafish tailbud is viscoelastic (elastic below a few seconds and fluid after just 1 min) and displays decreasing stiffness and increasing fluidity toward its posterior elongating region. This method opens new avenues to study mechanobiology in vivo, both in embryogenesis and in disease processes, including cancer.

| S-EPMC5524219 | biostudies-literature

Improved in vivo imaging method for individual islets across the mouse pancreas reveals a heterogeneous insulin secretion response to glucose.

Project description:While numerous techniques can be used to measure and analyze insulin secretion in isolated islets in culture, assessments of insulin secretion in vivo are typically indirect and only semiquantitative. The CpepSfGFP reporter mouse line allows the in vivo imaging of insulin secretion from individual islets after a glucose stimulation, in live, anesthetized mice. Imaging the whole pancreas at high resolution in live mice to track the response of each individual islet over time includes numerous technical challenges and previous reports were only limited in scope and non-quantitative. Elaborating on this previous model-through the development of an improved methodology addressing anesthesia, temperature control and motion blur-we were able to track and quantify longitudinally insulin content throughout a glucose challenge in up to two hundred individual islets simultaneously. Through this approach we demonstrate quantitatively for the first time that while isolated islets respond homogeneously to glucose in culture, their profiles differ significantly in vivo. Independent of size or location, some islets respond sharply to a glucose stimulation while others barely secrete at all. This platform therefore provides a powerful approach to study the impact of disease, diet, surgery or pharmacological treatments on insulin secretion in the intact pancreas in vivo.

| S-EPMC7804140 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data