Pattern of insulin delivery affects hepatic insulin sensitizing substance (HISS) action and insulin resistance

2004 ◽  
Vol 82 (12) ◽  
pp. 1068-1074 ◽  
Author(s):  
Maria A. G Reid ◽  
W Wayne Lautt
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Insulin Delivery ◽  
Glucose Disposal ◽  
Sprague Dawley ◽  
Fed State ◽  
Significant Difference ◽  
Bolus Insulin ◽  
Continuous Insulin Infusion

Hepatic insulin sensitizing substance (HISS) action accounts for 55% of the glucose disposal effect of a bolus of insulin in the fed state. To determine the effect of continuous versus pulsatile insulin delivery on HISS action in male Sprague–Dawley rats, insulin sensitivity was assessed using the rapid insulin sensitivity test (RIST) before and after a continuous, pulsatile, or bolus insulin (60 mU/kg i.v.) delivery. There was a significant difference in the RIST index after a continuous insulin infusion (247.9 mg/kg before, 73.2 mg/kg after) but not after 3 pulses where insulin action returned to baseline between pulses (211.6 mg/kg before, 191.0 mg/kg after) or single bolus (205.8 mg/kg before, 189.9 mg/kg after) insulin infusion. If a 3-pulse infusion was timed so that insulin action did not return to baseline between pulses, HISS action was suppressed. Continuous insulin infusion (10–30 min) showed progressive postinfusion blockade of HISS action. To maintain HISS-dependent insulin action, continuous insulin infusions should be avoided.Key words: pulsatile, glucose uptake, RIST, euglycemic clamp, insulin sensitivity.

Effects of daily physical activity on insulin action in the elderly

1992 ◽  
Vol 73 (6) ◽  
pp. 2241-2245 ◽  
Author(s):  
K. Yamanouchi ◽  
H. Nakajima ◽  
T. Shinozaki ◽  
K. Chikada ◽  
K. Kato ◽  
...  
Keyword(s):  
Physical Activity ◽  
Physical Training ◽  
Physical Inactivity ◽  
Insulin Action ◽  
Insulin Infusion ◽  
The Elderly ◽  
Daily Physical Activity ◽  
Young Athletes ◽  
Significant Difference ◽  
Insulin Responsiveness

The effects of daily physical activity on peripheral insulin action were investigated in aged individuals. Glucose infusion rates (GIR) during the euglycemic insulin clamp procedure in aged bedridden, aged controls, and aged athletes were compared with those in young controls and young athletes at insulin infusion rates of 40 and 400 mU.m-2.min-1 to estimate insulin action at physiological and maximal insulin concentrations, respectively. At both insulin infusion rates, GIR was significantly higher in aged athletes and significantly lower in aged bedridden subjects than in aged controls. Although there was no statistical difference in GIR at 400 mU.m-2 x min-1 between young athletes and young controls, GIR at 40 mU.m-2 x min-1 was higher in young athletes than in young controls. Comparison of the aged and young groups showed that although GIR at 400 mU.m-2 x min-1 was significantly lower in aged controls than in young controls, there was no significant difference between the aged athletes and the young athletes. We conclude that insulin responsiveness (insulin action at the postreceptor binding site) may decrease with the aging process and may be further affected by physical inactivity. Although physical training may improve insulin responsiveness in aged individuals up to levels similar to those in young athletes, physical training in young individuals may improve only insulin sensitivity.

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.

Rapid insulin sensitivity test (RIST)

1998 ◽  
Vol 76 (12) ◽  
pp. 1080-1086 ◽  
Author(s):  
W Wayne Lautt ◽  
Xiaowsi Wang ◽  
Parissa Sadri ◽  
Dallas J Legare ◽  
M Paula Macedo
Keyword(s):  
Insulin Sensitivity ◽  
Operating Procedure ◽  
Insulin Action ◽  
Standard Operating Procedure ◽  
Sensitivity Test ◽  
Bolus Administration ◽  
Venous Shunt ◽  
Technical Report ◽  
Significant Difference ◽  
Standard Operating

A rapid insulin sensitivity test (RIST) was recently introduced to assess insulin action in vivo (H. Xie, L. Zhu, Y.L. Zhang, D.J. Legare, and W.W. Lautt. J. Pharmacol. Toxicol. Methods, 35: 77-82. 1996). This technical report describes the current recommended standard operating procedure for the use of the RIST in rats based upon additional experience with approximately 100 tests. We describe the manufacture and use of an arterial-venous shunt that allows rapid multiple arterial samples and intravenous administration of drugs. The RIST procedure involves determination of a stable arterial glucose baseline to define the ideal euglycemic level to be maintained following a 5-min infusion of insulin, with the RIST index being the amount of glucose required to be infused to maintain euglycemia over the test period. Insulin administration by a 5-min infusion is preferable to a 30-s bolus administration. No significant difference was determined between the use of Toronto pork-beef or human insulin. Four consecutive RISTs were carried out in the same animal over 4-5 h with no tendency for change with time. The RIST index is sufficiently sensitive and reproducible to permit establishment of insulin dose-response curves and interference of insulin action by elimination of hepatic parasympathetic nerves, using atropine. This technical report provides the current recommended standard operating procedure for the RIST.Key words: insulin, resistance, test, methodology, glucose.

Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners

1996 ◽  
Vol 80 (1) ◽  
pp. 240-244 ◽  
Author(s):  
M. D. Vukovich ◽  
P. J. Arciero ◽  
W. M. Kohrt ◽  
S. B. Racette ◽  
P. A. Hansen ◽  
...  
Keyword(s):  
Infusion Rate ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Glucose Disposal ◽  
Inactive State ◽  
Transporter Protein ◽  
Glut 4 ◽  
Insulin Infusion Rate ◽  
Endurance Runners ◽  
Trained Runners

The purpose of this investigation was to determine whether decreased insulin action after 6 days of inactivity in endurance-trained runners was associated with a decrease in skeletal muscle glucose transporter protein levels (GLUT-4) in the gastrocnemius muscle. Seven endurance runners (5 men and 2 women) volunteered to participate in this investigation. All subjects had normal glucose tolerance as determined by the National Diabetes Data Group guidelines. Each individual completed two hyperinsulinemic euglycemic clamps at insulin infusion rates of 15 (LO) and 40 (HI) mU.m-2.min-1, one approximately 18 h after a training bout and the second after 6 days of inactivity (IA). Muscle biopsies for the measurement of GLUT-4 were obtained from the gastrocnemius before each clamp. Glucose disposal rates during the last 30 min of each insulin infusion were significantly reduced after 6 days of IA, averaging 6.45 +/- 1.04 mg.kg fat-free mass (FFM)-1.min-1 before and 4.55 +/- 0.56 mg.kg FFM-1.min-1 after detraining for the LO insulin infusion rate and 13.77 +/- 0.88 mg.kg FFM-1.min-1 before and 11.81 +/- 0.60 mg.kg FFM-1.min-1 after detraining for the HI insulin infusion rate (both P < 0.05), despite the fact that plasma insulin was higher in the inactive state (LO, 19.2 +/- 0.9 microU/ml before and 23.4 +/- 1.5 microU/ml after detraining; HI, 56.0 +/- 2.0 microU/ml before and 61.6 +/- 1.6 microU/ml after detraining; P < 0.05)). Calculated insulin clearance was greater in the trained than in the inactive state (P < 0.03). Muscle GLUT-4 transporter protein after 6 days of IA was reduced by 17.5 +/- 5.4% (P < 0.02). These results demonstrate that 6 days of IA reduces insulin action in endurance-trained runners and suggest that a reduction in muscle GLUT-4 transporter level plays a role in the decrease in glucose disposal rates.

scholarly journals Glucocorticoids and Insulin Sensitivity: Dissociation of Insulin’s Metabolic and Vascular Actions

2003 ◽  
Vol 88 (12) ◽  
pp. 6008-6014 ◽  
Author(s):  
C. G. Perry ◽  
A. Spiers ◽  
S. J. Cleland ◽  
G. D. O. Lowe ◽  
J. R. Petrie ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Action ◽  
Random Order ◽  
Glucose Disposal ◽  
High Dose ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Double Blind ◽  
High Dose Dexamethasone ◽  
Short Term Exposure ◽  
Healthy Males

Abstract Insulin sensitivity in tissues such as a skeletal muscle and fat is closely correlated with insulin action in the vasculature, but the mechanism underlying this is unclear. We investigated the effect of dexamethasone on insulin-stimulated glucose disposal and vasodilation in healthy males to test the hypothesis that a reduction in glucose disposal would be accompanied by a reduction in insulin action in the vasculature. We performed a double-blind, placebo-controlled, cross-over trial comparing insulin sensitivity (measured by the euglycemic hyperinsulinemic clamp) and vascular insulin action (measured by small vessel wire myography) in young healthy males allocated to placebo or 1 mg dexamethasone twice daily for 6 d, each in random order. Six days of dexamethasone therapy was associated with a 30% (95% confidence interval, 19.1–40.0%) fall in insulin sensitivity. Despite this, there was no difference in insulin-mediated vasodilation between phases. Dexamethasone had no effect on circulating markers of endothelial function, such as d-dimer, von Willebrand factor, and tissue plasminogen activator. By short-term exposure to high dose dexamethasone we were able to differentially affect the metabolic and vascular actions of insulin. This implies that, using this model, there is physiological uncoupling of the effects of insulin in different tissues.

scholarly journals Loss of PDGF-B activity increases hepatic vascular permeability and enhances insulin sensitivity

2011 ◽  
Vol 301 (3) ◽  
pp. E517-E526 ◽  
Author(s):  
Summer M. Raines ◽  
Oliver C. Richards ◽  
Lindsay R. Schneider ◽  
Kathryn L. Schueler ◽  
Mary E. Rabaglia ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Insulin Action ◽  
Basolateral Membrane ◽  
Tolerance Test ◽  
Whole Body ◽  
Glucose Disposal ◽  
Permeability Barrier ◽  
Loss Of Function ◽  
Transendothelial Transport

Hepatic vasculature is not thought to pose a permeability barrier for diffusion of macromolecules from the bloodstream to hepatocytes. In contrast, in extrahepatic tissues, the microvasculature is critically important for insulin action, because transport of insulin across the endothelial cell layer is rate limiting for insulin-stimulated glucose disposal. However, very little is known concerning the role in this process of pericytes, the mural cells lining the basolateral membrane of endothelial cells. PDGF-B is a growth factor involved in the recruitment and function of pericytes. We studied insulin action in mice expressing PDGF-B lacking the proteoglycan binding domain, producing a protein with a partial loss of function (PDGF-B ret/ ret). Insulin action was assessed through measurements of insulin signaling and insulin and glucose tolerance tests. PDGF-B deficiency enhanced hepatic vascular transendothelial transport. One outcome of this change was an increase in hepatic insulin signaling. This correlated with enhanced whole body glucose homeostasis and increased insulin clearance from the circulation during an insulin tolerance test. In obese mice, PDGF-B deficiency was associated with an 80% reduction in fasting insulin and drastically reduced insulin secretion. These mice did not have significantly higher glucose levels, reflecting a dramatic increase in insulin action. Our findings show that, despite already having a high permeability, hepatic transendothelial transport can be further enhanced. To the best of our knowledge, this is the first study to connect PDGF-B-induced changes in hepatic sinusoidal transport to changes in insulin action, demonstrating a link between PDGF-B signaling and insulin sensitivity.

scholarly journals Perbaikan Sensitivitas Insulin Diabetes Melitus Tipe 2 oleh Media Terkondisi Sel Punca Mesensimal

PRAXIS ◽  
2019 ◽  
Vol 1 (2) ◽  
pp. 180
Author(s):  
Bernadia Branitamahisi
Keyword(s):  
Insulin Sensitivity ◽  
T Test ◽  
Diabetic Rat ◽  
Control Group ◽  
Sprague Dawley ◽  
Type 2 Dm ◽  
Significant Difference ◽  
Type 2 Diabetic ◽  
Diabetes Melitus

Abstract: Type 2 diabetes mellitus is the highest prevalence among diabetes types, but there is no treatment that overcome obstacle in the process of surgery, rejection reactions, and increased complications that occur. The aim of this study was to investigate the insulin sensitivity improvement by Mesenchymal Stem Cell-Conditioned Medium(MSC-CM) through increased IRS-1 tyrosine phosphorylation (IRS-1tyr612) on the type 2 diabetic rat with and without treatment. This experimental study is purely laboratory Posttest Control Group using male Sprague Dawley rat, 7 weeks old and 150-200gram weight. Rat is divided into 3 research groups, K(-): normal control; K(+): diabetic control; P:treatment, type 2 DM rat+MSC-CM 0,1ml/200gBW ip. Giving MSC-CM is done every 3 days 10 times. On day 30 after therapy, an IRS-1tyr612 expression analysis was performed with skeletal muscle immunohistochemistry (IHC). Data analysis was performed by Kruskal-Wallis and Independent Sample T-test at 95% significance. Percentage of positive score of IRS-1tyr612 expression K(-)(75%)> P(62,5%)> K(+)(12,5%). Average expression of IRS-1tyr612 P(45,46±9,15)> K(-)(44,41±4,61)> K(+)(21,29±3,49) with significant difference of K(-)-K(+) and P-K(+). Giving MSC-CM may increase the expression of IRS-1tyr612 on type 2 diabetic animal model rat. Keywords: MSC-CM, insulin sensitivity, IRS-1tyr612, type 2 DM Abstrak: Diabetes melitus tipe 2 merupakan tipe diabetes dengan prevalensi tertinggi, namun belum ada pengobatan yang dapat mengatasi hambatan dalam proses operasi, reaksi rejeksi, dan banyaknya komplikasi yang terjadi. Penelitian ini bertujuan untuk mengetahui perbaikan sensitivitas insulin oleh Media Terkondisi Sel Punca Mesensimal (MT-SPM) melalui peningkatan fosforilasi tirosin 612 IRS-1(IRS-1tyr612) pada tikus model DM tipe 2 dengan dan tanpa terapi. Penelitian ini eksperimental murni laboratorium Posttest Control Group menggunakan hewan uji tikus Sprague Dawley jantan usia 7 minggu dan berat badan 150-200gram. Tikus dibagi menjadi 3 kelompok penelitian, yaitu K(-): kontrol normal; K(+): kontrol diabetik; P: perlakuan, tikus DM tipe 2 + MT-SPM 0,1ml/200g bb ip. Pemberian MT-SPM dilakukan setiap 3 hari sebanyak 10 kali. Pada hari ke-30 setelah terapi, dilakukan analisis ekspresi IRS-1tyr612 dengan IHC otot skelet. Analisis data dilakukan dengan Independent Sample T-test dan Kruskal Wallis pada signifikansi 95%. Prosentase skor positif ekspresi IRS-1tyr612 K(-)(75%) > P(62,5%) > K(+)(12,5%). Rerata ekspresi IRS-1tyr612 P(45,46±9,15) > K(-)(44,41±4,61) > K(+)(21,29±3,49) dengan perbedaan yang bermakna secara statistik pada K(-)–K(+) dan P–K(+). Pemberian MTSPM dapat meningkatkan ekspresi IRS-1tyr612 pada tikus model DM tipe 2. Kata kunci: MT-SPM, sensitivitas insulin, IRS-1tyr612,DM tipe 2

scholarly journals Effect of Bolus Insulin Administration Followed by a Continuous Insulin Infusion on Diabetic Ketoacidosis Management

Pharmacy ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 129
Author(s):  
Hannah Brown ◽  
Richard Tran ◽  
John Patka
Keyword(s):  
Diabetic Ketoacidosis ◽  
Insulin Infusion ◽  
Length Of Hospital Stay ◽  
Retrospective Chart Review ◽  
Regular Insulin ◽  
Bolus Administration ◽  
Emergency Department Admission ◽  
High Incidence ◽  
Bolus Insulin ◽  
Continuous Insulin Infusion

Despite the high incidence of diabetic ketoacidosis (DKA) there is no consensus on the most appropriate way to manage insulin therapy. This study was conducted to evaluate the effect of an insulin bolus on the resolution of DKA. A retrospective chart review of patients admitted between 1 September 2014 and 30 June 2016 with a diagnosis of DKA was conducted. Patients were assigned to the bolus or no bolus group based on provider preference. All patients were initiated on a 0.1 unit/kilogram (kg)/hour (h) intravenous (IV) regular insulin infusion, and patients in the bolus group were treated with a 0.1 unit/kg IV regular insulin bolus. Of the 145 admissions evaluated, 58 received a bolus and 87 did not. There was no difference in baseline demographics, except baseline blood glucose was higher in the bolus group (653 vs. 591 milligrams (mg)/deciliter (dL), p = 0.04). The time to resolution of DKA from emergency department admission did not differ between the bolus and no bolus group (15 vs. 15.9 h; p = 0.24). There was no difference in total insulin received (1.3 vs. 1.1 units/kg, p = 0.18), incidence of hypoglycemia (2 vs. 7%, p = 0.64), hypokalemia (16 vs. 29%, p = 0.65), or length of hospital stay (3.2 vs. 2.7 days, p = 0.27). The insulin bolus administration was not associated with reduced time to resolution of DKA.

Magnesium deficiency enhances basal glucose disposal in the rat

1995 ◽  
Vol 268 (5) ◽  
pp. E925-E931 ◽  
Author(s):  
P. Lowney ◽  
T. S. Hannon ◽  
A. D. Baron
Keyword(s):  
Insulin Infusion ◽  
Magnesium Deficiency ◽  
Dietary Treatment ◽  
Glucose Disposal ◽  
Sprague Dawley ◽  
Peripheral Tissues ◽  
Sprague Dawley Rats ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Glucose Disposal Rate

To investigate the contribution of hepatic and peripheral tissues to the enhanced glucose disposal rate (Kg) observed in magnesium (Mg)-deficient rats, euglycemic-hyperinsulinemic clamps were performed with continuous infusion of [3-3H]glucose and three insulin infusion rates, 1, 8, and 16 microU.kg-1.min-1. Moderately Mg-deficient (Mg-, 4.2 microM Mg/g diet) and Mg-adequate (Mg+, 16.7 microM Mg/g diet) Sprague-Dawley rats were studied after 3 wk of dietary treatment. Growth, fasting glucose, and insulin concentrations were not affected by dietary treatment. Basal hepatic glucose output (HGO) and glucose disposal (Rd) were increased by 24% in Mg- rats (P < 0.001). After 1 microU insulin.kg-1.min-1 infusion, Rd and the glucose infusion rate that maintained euglycemia were significantly increased in Mg- rats by 24 and 46%, respectively. However, when the increase in Rd above baseline was examined, no significant differences were observed. Therefore, the increased basal glucose disposal observed in Mg- rats may be mediated by noninsulin-dependent mechanisms. Insulin suppression of HGO during 1 microU insulin.kg-1.min-1 infusion was greater in Mg- rats (43%) compared with Mg+ rats (27%, P < 0.05). In conclusion, the increased Kg observed in Mg- rats is likely to be caused by an increase in noninsulin-mediated glucose uptake and an enhancement of hepatic insulin sensitivity.

Insulin action and secretion in endurance-trained and untrained humans

1987 ◽  
Vol 63 (6) ◽  
pp. 2247-2252 ◽  
Author(s):  
D. S. King ◽  
G. P. Dalsky ◽  
M. A. Staten ◽  
W. E. Clutter ◽  
D. R. Van Houten ◽  
...  
Keyword(s):  
Insulin Action ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Fat Free Mass ◽  
Glucose Disposal ◽  
Trained Subjects ◽  
Hyperglycemic Clamp ◽  
Significant Difference ◽  
Increased Sensitivity ◽  
Glucose Disposal Rate

To evaluate insulin sensitivity and responsiveness, a two-stage hyperinsulinemic euglycemic clamp procedure (insulin infusions of 40 and 400 mU.m-2.min-1) was performed on 11 endurance-trained and 11 untrained volunteers. A 3-h hyperglycemic clamp procedure (plasma glucose approximately 180 mg/dl) was used to study the insulin response to a fixed glycemic stimulus in 15 trained and 12 untrained subjects. During the 40-mU.m-2.min-1 insulin infusion, the glucose disposal rate was 10.2 +/- 0.5 mg.kg fat-free mass (FFM)-1.min-1 in the trained group compared with 8.0 +/- 0.6 mg.kg FFM-1.min-1 in the untrained group (P less than 0.01). In contrast, there was no significant difference in maximally stimulated glucose disposal: 17.7 +/- 0.6 in the trained vs. 16.7 +/- 0.7 mg.kg FFM-1.min-1 in the untrained group. During the hyperglycemic clamp procedure, the incremental area for plasma insulin was lower in the trained subjects for both early (0–10 min: 140 +/- 18 vs. 223 +/- 23 microU.ml–1.min; P less than 0.005) and late (10–180 min: 4,582 +/- 689 vs. 8,895 +/- 1,316 microU.ml–1.min; P less than 0.005) insulin secretory phases. These data demonstrate that 1) the improved insulin action in healthy trained subjects is due to increased sensitivity to insulin, with no change in responsiveness to insulin, and 2) trained subjects have a smaller plasma insulin response to an identical glucose stimulus than untrained individuals.

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