Porcine somatotropin alters insulin response in growing pigs by reducing insulin sensitivity rather than changing responsiveness

2012 ◽  
Vol 43 (1) ◽  
pp. 37-46 ◽  
Author(s):  
D. Wray-Cahen ◽  
F.R. Dunshea ◽  
R.D. Boyd ◽  
A.W. Bell ◽  
D.E. Bauman
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Response ◽  
Growing Pigs ◽  
Porcine Somatotropin

scholarly journals Effects of chromium supplementation on physiology, feed intake, and insulin related metabolism in growing pigs subjected to heat stress

2017 ◽  
Vol 1 (1) ◽  
pp. 116-125 ◽  
Author(s):  
F. Liu ◽  
J. J. Cottrell ◽  
U. Wijesiriwardana ◽  
F. W. Kelly ◽  
S. S. Chauhan ◽  
...  
Keyword(s):  
Heat Stress ◽  
Insulin Sensitivity ◽  
Respiration Rate ◽  
Rectal Temperature ◽  
Feed Intake ◽  
Insulin Response ◽  
Thermal Exposure ◽  
Growing Pigs ◽  
Model Assessment ◽  
Intravenous Glucose

Abstract Improving insulin sensitivity may reduce impacts of heat stress (HS) in pigs by facilitating heat dissipation. Chromium (Cr) has been reported to improve insulin sensitivity in pigs. Therefore, the aim of this experiment was to investigate whether Cr supplementation can mitigate HS in growing pigs. Thirty-six gilts were randomly assigned to 2 diets containing 0 (control) or 400 ppb Cr. After 14 d the supplemented pigs were allocated to either 8 d thermoneutral (20°C constant; TN) or cyclic HS (35°C, 0900 h to 1700 h) conditions and continued their respective diet (n = 9 per group). Growth performance was recorded during the 14-d supplementation period. The physiological responses to HS were monitored by measuring respiration rate, rectal temperature, blood gas chemistry, and feed intake during thermal exposure. Kinetics of plasma glucose, insulin and NEFA were studied by intravenous glucose tolerance test (IVGTT) on d 8 of thermal treatment. Results showed Cr alleviated the HS-increased rectal temperature (P < 0.05) and respiration rate (P < 0.01) at 1300 h and 1600 h during thermal exposure. However, Cr did not mitigate the reduction in average daily feed intake which was reduced by 35% during HS or the HS-induced respiratory alkalosis. Chromium tended to increase average daily gain (0.86 vs. 0.95 kg, P = 0.070) during the 14-d supplementation under TN conditions before thermal exposure, which might be associated with the potential of Cr in improving overall insulin sensitivity, as evidenced by a reduced insulin resistance index calculated by Homeostatic Model Assessment (HOMA-IR; 0.65 vs. 0.51, P = 0.013) and a tendency of reduced fasting plasma insulin concentration (1.97 vs. 1.67 μU/mL, P = 0.094). Heat stress decreased the acute insulin releasing rate (P = 0.012) and consequently slowed glucose clearance rate (P = 0.035) during IVGTT. Besides, HS enlarged the values of area under the curve of NEFA during IVGTT (P < 0.01), indicating a reduced lipid mobilization. In conclusion, HS reduced insulin response to IVGTT. Chromium supplementation exhibited a potential in improving insulin sensitivity and mitigating HS symptoms in growing pigs.

scholarly journals Regulation of Mitochondria-Associated Membranes (MAMs) by NO/sGC/PKG Participates in the Control of Hepatic Insulin Response

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1319 ◽  
Author(s):  
Arthur Bassot ◽  
Marie-Agnès Chauvin ◽  
Nadia Bendridi ◽  
Jingwei Ji-Cao ◽  
Guillaume Vial ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Soluble Guanylate Cyclase ◽  
Insulin Response ◽  
Cyclophilin D ◽  
Hepatic Insulin Sensitivity ◽  
Physiological Conditions ◽  
Huh7 Cells ◽  
The Impact

Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) upregulates hepatic insulin sensitivity. Recently, contact sites between the endoplasmic reticulum and mitochondria named mitochondria-associated membranes (MAMs) emerged as a crucial hub for insulin signaling in the liver. As mitochondria are targets of NO, we explored whether NO regulates hepatic insulin sensitivity by targeting MAMs. In Huh7 cells, primary rat hepatocytes and mouse livers, enhancing NO concentration increased MAMs, whereas inhibiting eNOS decreased them. In vitro, those effects were prevented by inhibiting protein kinase G (PKG) and mimicked by activating soluble guanylate cyclase (sGC) and PKG. In agreement with the regulation of MAMs, increasing NO concentration improved insulin signaling, both in vitro and in vivo, while eNOS inhibition disrupted this response. Finally, inhibition of insulin signaling by wortmannin did not affect the impact of NO on MAMs, while experimental MAM disruption, using either targeted silencing of cyclophilin D or the overexpression of the organelle spacer fetal and adult testis-expressed 1 (FATE-1), significantly blunted the effects of NO on both MAMs and insulin response. Therefore, under physiological conditions, NO participates to the regulation of MAM integrity through the sGC/PKG pathway and concomitantly improves hepatic insulin sensitivity. Altogether, our data suggest that the induction of MAMs participate in the impact of NO on hepatocyte insulin response.

scholarly journals Beneficial Effect of Diazoxide in Obese Hyperinsulinemic Adults1

1998 ◽  
Vol 83 (6) ◽  
pp. 1911-1915 ◽  
Author(s):  
Ramin Alemzadeh ◽  
Gina Langley ◽  
Lori Upchurch ◽  
Pam Smith ◽  
Alfred E. Slonim
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
Insulin Response ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Zucker Rats ◽  
Significant Difference

Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults [body mass index (BMI) > 30 kg/m2]. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean ± se for age and BMI, 31 ± 1 and 40 ± 2, respectively) received DZ (2 mg/kg BW·day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean± se for age and BMI, 28 ± 1 and 43 ± 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 ± 0.69% vs. 4.6 ± 0.61%, P < 0.001), greater decrease in body fat (P < 0.01), greater increase in fat-free mass to body fat ratio (P < 0.01), and greater attenuation of acute insulin response to glucose (P < 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified iv glucose tolerance test (Bergman’s minimal model) and no significant difference in glycohemoglobin values. Conclusion: 8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.

HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: a Multi-Center Cohort Study

2021 ◽  
Author(s):  
Rain Yamamoto ◽  
Majken K Jensen ◽  
Sarah Aroner ◽  
Jeremy D Furtado ◽  
Bernard Rosner ◽  
...  
Keyword(s):  
Cohort Study ◽  
Insulin Sensitivity ◽  
Clinical Investigation ◽  
Biological Effects ◽  
Sandwich Elisa ◽  
Insulin Response ◽  
Protein Composition ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Euglycemic Hyperinsulinemic Clamp

Abstract Context HDL in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. Objective We investigated the prospective associations between HDL subspecies containing and lacking apoC-III at baseline and insulin sensitivity at year 3. Design, Setting, and Participants A prospective cohort study of 864 healthy volunteers drawn from the RISC study, a multi-center European clinical investigation, whose recruitment initiated in 2002 with a follow-up of 3 years. Main Measures Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT) at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich ELISA-based method. Results The two HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (p-heterogeneity=0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (p-trend=0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (p-trend=0.01), compared to the lowest quintile. No significant association was observed for total HDL, and VLDL and LDL containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III. Conclusion Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.

Improved β-cell function after standardized weight reduction in severely obese subjects

2003 ◽  
Vol 284 (3) ◽  
pp. E557-E565 ◽  
Author(s):  
Marie Guldstrand ◽  
Bo Ahrén ◽  
Ulf Adamson
Keyword(s):  
Insulin Sensitivity ◽  
Weight Reduction ◽  
Cell Function ◽  
Insulin Response ◽  
Insulin Level ◽  
Glucagon Secretion ◽  
Obese Women ◽  
Β Cell ◽  
Β Cell Function ◽  
Severely Obese

Islet function was examined in 13 severely obese women [body mass index 46.4 ± 5.5 (SD) kg/m2] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR1), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37–50% after 15 and 25% WR ( P ≤ 0.05). Insulin sensitivity was determined as the amount of glucose infused to reach 14 mmol/l divided by the insulin level (M/I), a measure showing a linear correlation with insulin sensitivity during euglycemic hyperinsulinemic clamps ( r = 0.74, P < 0.001) and a hyperbolic relation to AIR1 ( r = −0.63, P < 0.001) in 169 healthy subjects. M/I was increased by 318 ± 182% after 15% ( P = 0.004) and by 489 ± 276% after 25% WR ( P = 0.007). The reduction in insulin secretion was not as large as anticipated from the increased insulin sensitivity, which resulted in an increased disposition index (DI; AIR1 × M/I). Thus DI increased by 95 ± 24% after 15% ( P = 0.018) and by 176 ± 35% after 25% WR ( P = 0.011). This improved β-cell function correlated independently with reduced glucose, triglycerides, and leptin and increased adiponectin levels and was associated with a reduced proinsulin-to-insulin ratio. In contrast, glucagon secretion was not significantly affected by WR. We conclude that WR results in improved β-cell function when related to insulin sensitivity.

Effect of sex and exogenous porcine somatotropin on longissimus muscle fiber characteristics of growing pigs.

1990 ◽  
Vol 68 (4) ◽  
pp. 1176-1181 ◽  
Author(s):  
M. B. Solomon ◽  
R. G. Campbell ◽  
N. C. Steele
Keyword(s):  
Muscle Fiber ◽  
Fiber Type ◽  
Live Weight ◽  
Growing Pigs ◽  
Fiber Types ◽  
Longissimus Muscle ◽  
Meat Tenderness ◽  
Giant Fiber ◽  
Porcine Somatotropin ◽  
Dose Levels

Abstract Thirty-seven pigs with an initial live weight of 60 kg were used to investigate the effects of daily exogenous porcine somatotropin (pST) administration at two dose levels (0 and 100 µg·kg−1·d−1) for a 31-d period on muscle fiber characteristics and meat tenderness of boars, gilts and barrows. Excipient boars and gilts had more αW and fewer αR fibers than did those receiving pST. The percentage of muscle fiber type for barrows was not affected by pST treatment. The administration of pST resulted in an increase in muscle fiber size for all three fiber types in all three sexes, but these changes were of greater magnitude in barrows (31.8%) and gilts (27.8%) than in boars (9.3%). Somatotropin negated the intrinsic sex effect differences in fiber area of the pigs. There was no difference in tenderness among excipient boars, barrows and gilts; however, with the inclusion of pST, shear force decreased in boars and gilts and increased in barrows. A high proportion of the pST-treated pigs contained giant fibers in the longissimus muscle. Furthermore, a small proportion of the pST-treated pigs exhibited pale, soft, exudative muscle. Whether the giant fiber anomalies occurred through increased muscle activity or from fibers undergoing degenerative changes was not determined.

Insulin sensitivity and fetal growth in ewes maintained in a moderate body condition compared with a lean body condition in late pregnancy

1997 ◽  
Vol 48 (6) ◽  
pp. 753 ◽  
Author(s):  
D. M. McNeill ◽  
R.W. Kelly ◽  
I. H. Williams
Keyword(s):  
Insulin Sensitivity ◽  
Body Condition ◽  
Body Condition Score ◽  
Insulin Response ◽  
Late Pregnancy ◽  
Similar Rate ◽  
Similar Amount ◽  
Fat Reserves ◽  
Exogenous Glucose ◽  
Condition Score

The possibility that an increase in maternal fatness might further enhance pregnancy-induced insulin insensitivity was investigated in ewes pregnant with one fetus. After selection of fat and lean ewes, they were fed to maintain maternal energy balance throughout pregnancy. A difference in insulin sensitivity of ewes in either a medium condition [score 2·9, 0·32± 0·031 kg fat/kg fat-free empty body (FFBW), n = 7] or lean body condition (score 2·0, 0·16±0.028 kg fat/kg FFBW, n = 8) at Day 136 of pregnancy was inferred by comparing their insulin response to an injection of glucose (350 mg/kg liveweight). The ewes were slaughtered at Day 146 of pregnancy to allow fetal weight, fetal fatness, and maternal fatness to be related to the capacity of the ewe to release insulin. The fatter ewes released more insulin in response to the injection of glucose (2. 54 log area units under the insulin response curve v. 2·22 for the lean ewes, pooled s.e. = 0·092, P < 0·05), yet cleared the glucose from their blood streams at the same rate as the leaner ewes. Because the fat ewes required more insulin to remove a similar amount of exogenous glucose at a similar rate to the lean ewes, we suggest that the fat ewes were less sensitive to insulin. Further, the fetuses of the fatter ewes, while not different in total weight, had higher levels of body fat than those of the leaner ewes (29·4 v. 23·8 g/kg FFBW, pooled s.e. r = 1·32, P < 0·05). Fetal fatness was also positively correlated to the magnitude of insulin release by the ewe (r = 0·61, P < 0·05). Since glucose is the major precursor of fetal fat, these data support our contention that a reduction in maternal insulin sensitivity, brought on by an increase in maternal fatness, could partition more glucose to the fetus. If fat reserves aid lamb survival, lambs from fat ewes rather than lean ewes may have a better chance of survival, particularly in cold conditions.

Modified protocols improve insulin sensitivity estimation using the minimal model

1987 ◽  
Vol 253 (6) ◽  
pp. E595-E602 ◽  
Author(s):  
Y. J. Yang ◽  
J. H. Youn ◽  
R. N. Bergman
Keyword(s):  
Standard Deviation ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Improve Insulin Sensitivity ◽  
Intravenous Glucose ◽  
Sensitivity Estimation ◽  
Model Technique

We attempted to improve the precision of the estimation of insulin sensitivity (S1) from the minimal model technique by modifying insulin dynamics during a frequently sampled intravenous glucose tolerance test (FSIGT). Tolbutamide and somatostatin (SRIF) were used to change the insulin dynamics without directly affecting insulin sensitivity. Injection of tolbutamide (100 mg) at t = 20 min provoked an immediate secondary peak in insulin response, resulting in a greater integrated incremental insulin than the standard FSIGT. SRIF, injected at t = -1 min, delayed insulin secretion in proportion to the dose without any change in magnitude. Computer simulation was used to assess the precision of S1 estimation. Insulin dynamics from both standard and modified protocols were adjusted in magnitude, with the shape unchanged and analyzed to determine the effect of the magnitude of insulin response. Fractional standard deviation was reduced from 73% with the standard insulin profile to 23% with tolbutamide and 18% with the highest dose of SRIF. In addition, the fractional standard deviation of S1 estimates decreased exponentially with increasing magnitude of insulin response. Modified FSIGTs require a smaller insulin response than the standard protocol to achieve the same precision.

scholarly journals Shotgun Lipidomics Discovered Diurnal Regulation of Lipid Metabolism Linked to Insulin Sensitivity in Nondiabetic Men

2019 ◽  
Vol 105 (5) ◽  
pp. 1501-1514 ◽  
Author(s):  
Katharina Kessler ◽  
Mathias J Gerl ◽  
Silke Hornemann ◽  
Markus Damm ◽  
Christian Klose ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Diurnal Variation ◽  
Saturated Fatty Acids ◽  
Insulin Response ◽  
Time Of Day ◽  
Diurnal Changes ◽  
High Fat ◽  
Shotgun Lipidomics ◽  
Meal Timing

Abstract Context Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied. Objective We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control. Design 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order. Results 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion. Conclusions This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity.

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