scholarly journals Leptin and Its Relation to Obesity and Insulin in the SHR/N-corpulent Rat, A Model of Type II Diabetes Mellitus

2001 ◽  
Vol 2 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Manuel T. Velasquez ◽  
Sam J. Bhathena ◽  
Carl T. Hansen

The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic animal model that exhibits obesity, metabolic features of hyperinsulinemia, hyperglycemia, and hyperlipidemia, which are characteristic of type II diabetes and mild hypertension. To determine the role of leptin, the protein product of theobgene, in the development of obesity and diabetes in this model, we measured steady-state circulating levels of leptin in obese and lean SHR/N-cp rats and examined the relation between plasma leptin levels and metabolic variables at the stage of established obesity in these animals. Mean fasting plasma leptin concentration was 8-fold higher in obese than in lean rats (p<0.01). This was associated with a 6-fold elevation in plasma insulin in the obese group. Fasting levels of plasma glucose, cholesterol, and triglyceride were all significantly higher in obese rats than in lean controls. Spearman correlation analysis showed a significant positive correlation between plasma leptin concentration and body weight among the animals (r=0.73, p<0.01). Similarly, plasma insulin concentration was significantly correlated with BW in all animals (r=0.54, p<0.05). There was also a significant positive.correlation between plasma leptin and plasma insulin in the entire group (r=0.70, p<0.01). However, this relationship was significant only for lean rats but not for obese rats (r=0.59, p<0.05 for lean rats, and r=0.23, p=NS, for obese rats). Plasma leptin also correlated positively with fasting plasma glucose (r=0.75, p<0.05), total cholesterol (r=0.63, p<0.05), and triglyceride (r=0.67, p <0.05). The marked elevation of plasma leptin in obese SHR/N-cp rats suggests that obesity in this animal model is related to up-regulation of the ob gene. Circulating leptin appears to be one of the best biological markers of obesity and that hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in the diabesity syndrome.

2019 ◽  
Vol 16 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Anirudh Kumar ◽  
Divyang R Patel ◽  
Kathy E Wolski ◽  
A Michael Lincoff ◽  
Sangeeta R Kashyap ◽  
...  

Background: Despite optimal treatment, type II diabetes mellitus remains associated with an increased risk for future cardiovascular events. We sought to determine the association between baseline fasting plasma insulin levels and major adverse cardiovascular outcomes in patients with type II diabetes mellitus and high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial. Methods: We included all patients with type II diabetes mellitus who had a central laboratory measured fasting plasma insulin level drawn at baseline as part of the study protocol. Hazard ratios were generated for the risk of major adverse cardiovascular outcomes (composite of cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina and coronary revascularization) with increasing quartile of baseline fasting plasma insulin level. We then performed a multivariable regression adjusting for significant baseline characteristics. Results: Among 12,092 patients in ACCELERATE, 2042 patients with type II diabetes mellitus had a baseline fasting plasma insulin level drawn. Median follow-up was 28 months. The study population had a mean age of 66.6 years, 79.2% male and 96.2% had established coronary artery disease. During follow-up, major adverse cardiovascular outcomes occurred in 238 patients (11.6%); of these events, 177 were coronary revascularization (8.7%). We observed a statistically significant relationship between rates of revascularization and rising quartile of baseline fasting plasma insulin level which was not noted for the other individual components of major adverse cardiovascular outcomes. Patients with type II diabetes mellitus who underwent revascularization were noted to have significantly higher baseline fasting plasma insulin levels (27.7 vs 21.4 mU/L, p-value = 0.009) although baseline haemoglobin A1c (6.63% vs 6.55%), body mass index (31.5 vs 31.1 kg/m2) and medical therapy were otherwise similar to the group not undergoing revascularization. Following multivariable regression adjusting for significant characteristics including exposure to evacetrapib, the log of baseline fasting plasma insulin level was found to be an independent predictor for major adverse cardiovascular outcomes (hazard ratio = 1.36, 95% confidence interval = 1.09–1.69, p-value = 0.007); this was driven by need for future revascularization (hazard ratio = 1.56, 95% confidence interval = 1.21–2.00, p-value = 0.001). Conclusion: In a contemporary population of patients with type II diabetes mellitus and high-risk vascular disease on optimum medical therapy, baseline hyperinsulinaemia was an independent predictor for major adverse cardiovascular outcomes and need of future coronary revascularization. These results suggest a pathophysiological link between hyperinsulinaemia and progression of atherosclerotic vascular disease among diabetics.


2018 ◽  
Vol 9 (4) ◽  
pp. 143
Author(s):  
Adediji Isaac Oluwole ◽  
Ayodele Ademola Adelakun ◽  
Afolabi Joy Oluwaseyifunmi ◽  
Akinleye Waheed A ◽  
Taiwo Timilehin Darasimi

Background: Type II DM and obesity are metabolic disorders characterized by insulin resistance, dyslipidaemia, and metabolic stress. These features were assessed in patients using fasting plasma glucose, fasting lipid profile and serum cortisol as their markers.Materials and methods: Ninety participants were recruited and classified into 3 groups of thirty each – Obese with type II DM, Non-obese with type II DM, non-obese and non-diabetics who served as controls. Anthropometric measures of weight and height were taken using standard procedures and body mass index was calculated thereafter. Blood samples were collected after an overnight fast for the in vitro assay of serum cortisol, plasma glucose, triglycerides, total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol using enzyme linked immunosorbent assay and colorimetry as appropriate. Data obtained were analyzed statistically using ANOVA and post hoc test for comparison of variables between groups. Pearson’s correlation was performed to assess the relationship between variables and p<0.05 was considered significant.Results: Serum cortisol, plasma glucose, total cholesterol, triglycerides and LDL-cholesterol were elevated while HDL-cholesterol was reduced in both obese and non-obese subjects with type II diabetes mellitus when compared with controls. Cortisol had a significant positive association with plasma glucose, total cholesterol, triglycerides and LDL-cholesterol in obese subjects with type II diabetes mellitus while cortisol had a significant inverse relationship with HDL-cholesterol in both obese and non-obese subjects with type II diabetes mellitus.Conclusion: From this study, we conclude that elevated serum cortisol, a consequence of type II DM, accompanies dyslipidaemia in both obese and non-obese type II DM patients. It could therefore be inferred that ‘diabetic stress’ is the underlying factor of elevated cortisol in this group.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammad Badran ◽  
Ismail Laher

The global epidemic of diabetes has not spared the Arabic-speaking countries, which have some of the highest prevalence of type II diabetes. This is particularly true of the Arab Gulf, a conglomerate of high income, oil-producing countries where prevalence rates are the highest. The prevalence rates among adults of the Arabic speaking countries as a whole range between 4%–21%, with the lowest being in Somalia and the highest in Kuwait. As economic growth has accelerated, so has the movement of the populations to urban centers where people are more likely to adopt lifestyles that embrace increased high-calorie food consumption and sedentary lifestyles. These factors likely contribute to the increased prevalence of obesity and diabetes in the Arabic speaking countries.


Diabetologia ◽  
2001 ◽  
Vol 44 (6) ◽  
pp. 700-705 ◽  
Author(s):  
R. L. Perrott ◽  
R. V. North ◽  
N. Drasdo ◽  
K. A. Ahmed ◽  
D. R. Owens

2011 ◽  
Vol 96 (6) ◽  
pp. 1763-1770 ◽  
Author(s):  
E. Cersosimo ◽  
A. Gastaldelli ◽  
A. Cervera ◽  
E. Wajcberg ◽  
A. Sriwijilkamol ◽  
...  

Objective: Our objective was to examine the mechanisms via which exenatide attenuates postprandial hyperglycemia in type 2 diabetes mellitus (T2DM). Study Design: Seventeen T2DM patients (44 yr; seven females, 10 males; body mass index = 33.6 kg/m2; glycosylated hemoglobin = 7.9%) received a mixed meal followed for 6 h with double-tracer technique ([1-14C]glucose orally; [3-3H]glucose iv) before and after 2 wk of exenatide. In protocol II (n = 5), but not in protocol I (n = 12), exenatide was given in the morning of the repeat meal. Total and oral glucose appearance rates (RaT and RaO, respectively), endogenous glucose production (EGP), splanchnic glucose uptake (75 g − RaO), and hepatic insulin resistance (basal EGP × fasting plasma insulin) were determined. Results: After 2 wk of exenatide (protocol I), fasting plasma glucose decreased (from 10.2 to 7.6 mm) and mean postmeal plasma glucose decreased (from 13.2 to 11.3 mm) (P &lt; 0.05); fasting and meal-stimulated plasma insulin and glucagon did not change significantly. After exenatide, basal EGP decreased (from 13.9 to 10.8 μmol/kg · min, P &lt; 0.05), and hepatic insulin resistance declined (both P &lt; 0.05). RaO, gastric emptying (acetaminophen area under the curve), and splanchnic glucose uptake did not change. In protocol II (exenatide given before repeat meal), fasting plasma glucose decreased (from 11.1 to 8.9 mm) and mean postmeal plasma glucose decreased (from 14.2 to 10.1 mm) (P &lt; 0.05); fasting and meal-stimulated plasma insulin and glucagon did not change significantly. After exenatide, basal EGP decreased (from 13.4 to 10.7 μmol/kg · min, P = 0.05). RaT and RaO decreased markedly from 0–180 min after meal ingestion, consistent with exenatide's action to delay gastric emptying. Conclusions: Exenatide improves 1) fasting hyperglycemia by reducing basal EGP and 2) postmeal hyperglycemia by reducing the appearance of oral glucose in the systemic circulation.


Sign in / Sign up

Export Citation Format

Share Document