Effects of age and anesthetic on plasma glucose and insulin levels and insulin sensitivity in spontaneously hypertensive and Wistar rats

2002 ◽  
Vol 80 (10) ◽  
pp. 962-970 ◽  
Author(s):  
Erika R Vera ◽  
Mary L Battell ◽  
Sanjay Bhanot ◽  
John H McNeill

We examined the effects of anesthetic, age, and strain on oral glucose tolerance tests (OGTT, 1 g/kg body weight) and intraperitoneal glucose tolerance tests (IPGTT, 2 g/kg body weight) in spontaneously hypertensive (SH) and Wistar rats. Pentobarbital anesthesia caused an elevation in basal glucose and insulin levels in Wistar rats at 9 and 16 weeks of age and in SH rats at 9 weeks. Anesthesia increased the insulin output during an OGTT in both strains of rats while glucose was unchanged. Anesthesia reduced the insulin sensitivity index calculated from the OGTT but not from the IPGTT data. The age of the rats (9–11 vs. 16–18 weeks) had no effect on the basal glucose or insulin levels, but older Wistar rats had a greater insulin output following oral glucose and older SH rats had a greater insulin output following intraperitoneal glucose. On the basis of the insulin sensitivity index, SH rats were clearly more insulin resistant than age-matched Wistar rats. The SH rats also had higher basal insulin levels, as well as higher insulin output, following both glucose challenges. In summary, SH rats are more insulin resistant than Wistar rats, and anesthesia, which elevated basal glucose and insulin levels and increased the insulin output in response to a glucose challenge, may increase insulin resistance.Key words: spontaneously hypertensive rats, insulin sensitivity index, anesthesia, age.

2008 ◽  
Vol 158 (5) ◽  
pp. 711-719 ◽  
Author(s):  
S Cupisti ◽  
N Kajaia ◽  
R Dittrich ◽  
H Duezenli ◽  
M W Beckmann ◽  
...  

BackgroundThe aim of this study was to evaluate associations of clinical features, such as hirsutism, polycystic ovaries (PCOs), ovulatory dysfunction, and body mass index (BMI) ≥25 kg/m2, with metabolic abnormalities in hyperandrogenic women.MethodsHirsutism was based on the modified Ferriman–Gallwey score. Ovulatory function was classified as eumenorrhea, oligomenorrhea and amenorrhea, and PCOs were assessed using the ultrasound criteria recommended in the Rotterdam definition. An oral glucose tolerance test was performed. Different insulin resistance (IR) indices were calculated.ResultsHirsute women had significantly higher BMI, DHEA sulfate (DHEAS) and free androgen index (FAI), and significantly lower values for sex hormone-binding globulin (SHBG). Women with amenorrhea were younger in comparison to women with eumenorrhea and had significantly higher values for fasting insulin (FI) and 1- and 2-h insulin levels; lower values for glucose to insulin ratio (GIR), quantitative insulin sensitivity check index (QUICKI), and SHBG. Women with PCO had significantly higher levels of LH and low-density lipoprotein (LDL), whereas high-density lipoprotein (HDL) levels were significantly lower. Women with a BMI ≥25 kg/m2 had significantly higher values for age, fasting plasma glucose, FI, and 1- and 2-h glucose and insulin levels, homeostatic model for assessment of IR (HOMA-IR), homeostatic model for assessment of B-cell function (HOMA-B), and FAI, whereas their GIR, insulin sensitivity index, QUICKI, SHBG, and HDL were significantly lower.ConclusionsIn women with hyperandrogenic syndrome, BMI≥25 kg/m2 and amenorrhea appear to be associated with severe endocrine and metabolic abnormalities.


2004 ◽  
Vol 89 (3) ◽  
pp. 1096-1101 ◽  
Author(s):  
Catherine W. Yeckel ◽  
Ram Weiss ◽  
James Dziura ◽  
Sara E. Taksali ◽  
Sylvie Dufour ◽  
...  

Abstract Given the extreme increase in prediabetes, type 2 diabetes, and the potential for metabolic syndrome in obese youth, identifying simplified indexes for assessing stimulated insulin sensitivity is critical. The purpose of this study was validation of two surrogate indexes of insulin sensitivity determined from the oral glucose tolerance test (OGTT): the composite whole body insulin sensitivity index (WBISI) and the insulin sensitivity index (ISI). An obese population (aged 8–18 yr) of normal and impaired glucose tolerance individuals was studied. One group (n = 38) performed both the euglycemic-hyperinsulinemic clamp and OGTT for comparison of insulin sensitivity measurements as well as 1H-magnetic resonance spectroscopy estimates of intramyocellular lipid content. Another larger (n = 368) cohort participated only in an OGTT. Both the WBISI and ISI represented good estimates (r = 0.78 and 0.74; P < 0.0005) for clamp-derived insulin sensitivity (glucose disposed, M-value), respectively. In the large cohort, the surrogate indexes demonstrated the shift toward poorer function and increased risk profile as a function of insulin resistance. Additionally, the WBISI and ISI correlated with intramyocellular lipid content (r = −0.74 and −0.71; P < 0.0001), a tissue marker for insulin resistance. Insulin sensitivity can be estimated using plasma glucose and insulin responses derived from the OGTT in obese youth with normal and impaired glucose tolerance.


CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 316-316
Author(s):  
William Martin ◽  
Christine Graham ◽  
Linda Morrow ◽  
Carine Beysen ◽  
Frederico G.S. Toledo ◽  
...  

Abstract:Background:A combination of olanzapine and samidorphan (OLZ/SAM) is in development for schizophrenia to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The objective of this phase 1 exploratory study was to assess metabolic treatment effects of OLZ/SAM.Methods:Healthy, non-obese adults (18–40 years) were randomized 2:2:1 to once-daily OLZ/SAM, olanzapine, or placebo for 21 days. Assessments included oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, weight gain, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance.Results:Sixty subjects were randomized (OLZ/SAM, n=24; olanzapine, n=24; placebo, n=12); 19 (79.2%), 22 (91.7%), and 11 (91.7%), respectively, completed the study. In the OGTT, olanzapine led to significant hyperinsulinemia (P<0.0001) and significantly reduced insulin sensitivity (2-hour Matsuda index) at day 19 vs baseline (P=0.0012), changes not observed with OLZ/SAM. No significant between-group differences were observed for change from baseline in clamp-derived insulin sensitivity index at day 21. Least squares mean weight change from baseline was similar with OLZ/SAM (3.16 kg) and olanzapine (2.87 kg); both were significantly higher than placebo (0.57 kg; both P<0.01). Caloric intake significantly decreased from baseline to day 22 with OLZ/SAM (P=0.015) but not with olanzapine or placebo. Forty-nine subjects (81.7%) experienced ≥1 AE (OLZ/SAM, 87.5%; olanzapine, 79.2%; placebo, 75.0%).Conclusions:In this exploratory study, hyperinsulinemia and decreased insulin sensitivity were observed in the OGTT with olanzapine but not with OLZ/SAM or placebo. Clamp-derived insulin sensitivity index and weight changes were similar with OLZ/SAM and olanzapine in healthy subjects during the 3-week study.Funding Acknowledgements:This study was funded by Alkermes, Inc.


2003 ◽  
Vol 88 (3) ◽  
pp. 1019-1023 ◽  
Author(s):  
Supamai Soonthornpun ◽  
Worawong Setasuban ◽  
Atchara Thamprasit ◽  
Wanne Chayanunnukul ◽  
Chatchalit Rattarasarn ◽  
...  

Reumatismo ◽  
2018 ◽  
Vol 70 (4) ◽  
pp. 232-240 ◽  
Author(s):  
M. Bellan ◽  
S. Bor ◽  
A. Gibbin ◽  
A. Gualerzi ◽  
S. Favretto ◽  
...  

Whether the insulin resistance commonly observed in patients with inflammatory arthritis is a disease-specific feature and/or is limited to a disease phase (i.e., it occurs only during phases of high disease activity) is unknown. Fifty-three rheumatoid arthritis (RA) and 44 psoriatic arthritis (PsA) patients were recruited consecutively along with 194 controls matched for age, sex and body mass index for a case-control study. All underwent an oral glucose tolerance test, the results of which were analysed to derive the following indexes: homeostatic model of insulin resistance (HOMA-IR), insulin sensitivity index (ISI) and early insulin sensitivity index (EISI). These data were related to anthropometric, clinical and laboratory findings. Metabolic parameters of patients and controls were similar. Neither inflammatory markers nor disease activity scores were related to glucose metabolism for the generality of RA and PsA patients; however, by restricting the analysis to the subset of RA patients with residual disease activity, an association emerged between erythrocyte sedimentation rate, on the one hand, and fasting insulin (β=0.46, p=0.047) and HOMA-IR (β=0.44, p=0.02), on the other. Moreover, C-reactive protein (CRP) levels were associated with plasma glucose and insulin levels measured 120 min after the glucose load (β=0.91, p=0.0003 and β=0.77, p=0.0006, respectively); ISI and EISI were predicted by CRP (β=-0.79, p=0.0006; β=-0.80, p=0.0001, respectively). The same did not hold true for PsA patients. The association between systemic inflammation and insulin resistance indexes is a feature of RA with residual disease activity, not a universal feature of inflammatory arthritides.


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