Higher Fasting Serum Insulin Levels Research Articles

The gallbladder in diabetes

The gallbladder in diabetes

Transgenic expression of the positive selected human GLUD2 gene improves in vivo glucose homeostasis by regulating basic insulin secretion

Glutamate dehydrogenase 1 (GDH1) contributes to glucose-stimulated insulin secretion in murine β-cells, but not to basic insulin release. The implications of these findings for human biology are unclear as humans have two GDH-specific enzymes: hGDH1 (GLUD1-encoded) and hGDH2 (GLUD2-encoded), a novel enzyme that is highly activated by ADP and L-leucine. Here we studied in vivo glucose homeostasis in transgenic (Tg) mice generated by inserting the GLUD2 gene and its putative regulatory elements into their genome. Using specific antibodies, we observed that hGDH2 was co-expressed with the endogenous murine GDH1 in pancreatic β-cells of Tg mice. Fasting blood glucose (FBG) levels were lower and of a narrower range in Tg (95% CI: 90.6–96.8 mg/dl; N = 26) than in Wt mice (95% CI: 136.2–151.4 mg/dl; N = 23; p < 0.0001), closely resembling those of healthy humans. GLUD2 also protected the host mouse from developing diabetes with advancing age. Tg animals maintained 2.6-fold higher fasting serum insulin levels (mean ± SD: 1.63 ± 0.15 ng/ml; N = 12) than Wt mice (0.63 ± 0.05 ng/ml; N = 12; p < 0.0001). Glucose loading (1 mg/g, given i.p.) induced comparable serum insulin increases in Tg and Wt mice, suggesting no significant GLUD2 effect on glucose-stimulated insulin release. L-leucine (0.25 mg/g given orally) induced a 2-fold increase in the serum insulin of the Wt mice, implying significant activation of the endogenous GDH1. However, L-leucine had little effect on the high insulin levels of the Tg mice, suggesting that, under the high ADP levels that prevail in β-cells in the fasting state, glutamate flux through hGDH2 is close to maximal. Hence, the present data, showing that GLUD2 expression in Tg mice improves in vivo glucose homeostasis by boosting fasting serum insulin levels, suggest that evolutionary adaptation of hGDH2 has enabled humans to achieve narrow-range euglycemia by regulating glutamate-mediated basal insulin secretion.

Alpha-Linolenic Acid-Enriched Diacylglycerol Oil Suppresses the Postprandial Serum Triglyceride Level-A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

This study investigated the effect of a single oral ingestion of alpha-linolenic acid-enriched diacylglycerol (ALA-DAG) on postprandial serum triglyceride (TG) levels. A randomized, double-blind, controlled, crossover study was performed in subjects with normal or moderately high fasting serum TG levels. Subjects ingested 0.00 g [control: triacylglycerol; TAG (rapeseed oil)], 1.25 g (1.25-g: mixture of 1.25 g ALA-DAG and 1.25 g TAG), or 2.50 g (2.50 g) of ALA-DAG in random order with a 6-d washout period. Serum TG levels were evaluated in the fasting state, and at 2, 3, 4, and 6 h after the test meal. Thirty-eight subjects completed the study and were defined as the per protocol set. As the primary outcome, postprandial serum TG levels were significantly lower in the 2.50-g treatment compared with the control. The TG level did not differ significantly between the 1.25-g and control. The suppressive effect of ALA-DAG on the serum TG level correlated significantly with the body mass index and fasting insulin level. ALA-DAG at a dose of 2.50 g had greater effects on serum TG and apolipoprotein B levels in subjects with a higher body mass index (≥25 kg/m2) and higher fasting serum insulin levels (>10 μU/mL). Our findings suggest that ingesting 2.50 g ALA-DAG suppresses the postprandial serum TG level in people with normal and moderately high fasting serum TG levels, presumably as a result of poor re-esterification of dietary fat into TG in the intestinal mucosa.

Association of the β 3-adrenergic receptor Trp64Arg polymorphism with common metabolic traits: Studies of 7605 middle-aged white people

Aim/hypothesis The functional variant Trp64Arg in the β 3-adrenergic receptor has previously been examined for association with obesity and insulin resistance with ambiguous results. For further evaluation the present study examined the impact of the Trp64Arg variant on the pathogenesis of type 2 diabetes and obesity in a relatively large, homogenous study population. Methods The Trp64Arg polymorphism was genotyped in 7605 Danish subjects using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Association was examined in case-control studies of obesity (1529 cases and 6049 controls) and type 2 diabetes (1373 cases and 4742 controls) and quantitative trait analyses among 5822 individuals. Furthermore, the association of Trp64Arg with type 2 diabetes was examined in a meta-analysis. Results The Trp64Arg polymorphism was not associated with obesity. However, the Arg-allele was associated with a slightly increased risk of type 2 diabetes (OR1.15 (CI: 1.01–1.31); p = 0.04), increased insulin resistance estimated by homeostasis model assessment ( p = 0.01), higher fasting serum insulin levels ( p = 0.01), and higher levels of plasma glucose 2-h after glucose ingestion ( p = 0.02). After sex stratification these associations were only present among women. Furthermore, the Arg-allele was borderline associated with type 2 diabetes in a meta-analysis of the present and 26 previous studies ( p = 0.06, OR1.27 (CI: 0.99–1.63)) ( n = 18891). Conclusion/interpretation Trp64Arg does not confer an increased risk of obesity among Danes. Yet, in the present study of 7605 Danes the variant is associated with type 2 diabetes and quantitative traits related to type 2 diabetes.

Direct metabolic effects of risperidone and olanzapine in Japanese schizophrenic patients

Direct metabolic effects of risperidone and olanzapine in Japanese schizophrenic patients

Sexual dimorphism in insulin sensitivity and susceptibility to develop diabetes in rats

The goal of this study was to evaluate gender-related differences of some metabolic determinants of insulin sensitivity and of susceptibility to the effects of diabetes. Changes in body weight, blood glucose, and serum insulin concentrations were compared between female and male Wistar rats in prepubertal, pubertal, and adult stages of life. A diabetic model was induced by streptozotocin (STZ) under nicotinamide protection in both sexes and metabolic patterns were evaluated during the next 4 weeks. Finally, the pancreases were processed for morphometric analysis. In the three age groups, at similar blood glucose levels, higher fasting serum insulin levels were found in female as compared with age matched male rats. After STZ treatment, female rats show lower insulin and higher glucose levels, and a worse survival rate as compared with male rats. The more severe disease phenotype observed in female animals is associated with a more dramatic perturbation of pancreatic islet morphology. Significant differences exist in insulin sensitivity between sexes, females being less sensitive to insulin than males at all age groups and more susceptible to the rapid development of a more severe form of diabetes than males.

Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia

Objective Recent studies have suggested a beneficial role of insulin on brain function and psychological well-being. This study was undertaken to examine whether fasting serum insulin levels are associated with the psychopathology profile in a cross-sectional sample of acutely ill non-diabetic inpatients with schizophrenia. Methods Subjects were recruited from a county hospital. Each subject underwent a psychopathology assessment with the Positive and Negative Syndrome Scale (PANSS). A fasting blood sample was taken to measure serum insulin, plasma glucose and lipids. Results Twenty-six subjects (7 females, 19 males) were included in the study. Pearson correlation analysis showed significant inverse relationships between serum insulin level and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores ( r = − 0.41, p = 0.037; r = − 0.49, p = 0.010; r = − 0.45, p = 0.023, respectively). However, there was no significant relationship between serum insulin level and PANSS-Negative Symptom subscale score ( r = − 0.13, p = 0.53). Partial correlation analysis showed that the inverse relationships between serum insulin levels and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores became even stronger after controlling for potential confounding variables including age, gender, race, family history of mental illness, age of illness onset and body-mass index (BMI). Conclusions Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia. It is speculated that insulin might improve clinical symptoms of schizophrenia by interacting with dopamine and other neurotransmitter systems.

Growth hormone secretion and insulin-like growth factor-1 are related to hyperandrogenism in nonobese patients with polycystic ovary syndrome

Women of normal weight with polycystic ovary syndrome (PCOS) and hyperinsulinemia presented high growth hormone (GH) levels in response to the l-dopa test, suggesting that the action of GH and insulin-like growth factor-1 (IGF-1) might be responsible for the elevation in LH and the consequent hyperandrogenic anovulation observed in normal weight women with PCOS. Insulin resistance and obesity are related to a reduction in GH secretion in obese women with PCOS.

Serum growth hormone and insulin but not insulin-like growth factor-1 levels are elevated in patients with fibromyalgia syndrome

Standard radioimmunoassay (RIA) was employed to quantify basal serum growth hormone (GH), insulin-like growth factor-I (IGF-1), and insulin levels in 32 normoglycemic patients with clinically active fibromyalgia and in 29 normoglycemic control subjects. The GH concentration was significantly higher (P < 0.001) in female fibromyalgia patients than age-matched, normal female subjects. In contrast, basal serum IGF-1 concentrations did not differ between these groups. A scatter plot generated from two-stage, least-squares analysis showed that serum GH lacked correlation with the serum IGF-1 concentrations of normal female subjects (P = 0.73) and female fibromyalgia patients (P = 0.19). In addition to the results from serum GH and IGF-1 RIA, we also found significantly higher fasting serum insulin levels (P = 0.03) in male fibromyalgia patients and a trend toward elevated fasting serum insulin levels in the female fibromyalgia population ( P = 0.07), with the mean fasting level in the male fibromyalgia group (35.7 microU/ml(-1)) exceeding the upper limit of normal serum insulin levels (i.e., 27 microU/ml(-1)). Based on these results, basal serum GH and fasting serum insulin levels appear to be valuable surrogate markers in clinically active, normoglycemic fibromyalgia patients.

The relationship between the 'metabolic score' and sub-clinical atherosclerosis detected with electron beam computed tomography.

This study examines the contribution of the metabolic syndrome, as defined by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), to sub-clinical atherosclerosis and the cardiovascular risk assessment in an asymptomatic screening population. We studied 1000 consecutive, asymptomatic, apparently healthy men and women aged 40-45 years, enrolled into a prospective cardiovascular risk assessment study. The 'metabolic score' (MS) was calculated as the sum of the five metabolic syndrome risk factors defined per NCEP III. The metabolic syndrome was defined as a metabolic score >/=3. Coronary artery calcification (CAC) on electron beam computed tomography (EBCT) was used to measure sub-clinical atherosclerosis. The prevalence of the metabolic syndrome was 8.9% (89/999), and was associated with significantly higher fasting serum insulin levels and significantly lower activity indices. Participants with the metabolic syndrome were more likely to have a positive CAC score 24.7% (24 of 89) compared to those without 16.5% (159 of 910, P<0.05.) After controlling for serum low-density lipoprotein, the metabolic score and the metabolic syndrome remained a significant independent predictor of sub-clinical atherosclerosis. The 'metabolic score' is a simple clinical measurement that directly and independently relates to the likelihood of premature sub-clinical calcified atherosclerosis in an asymptomatic screening population.

Hypertension and the Metabolic Cardiovascular Syndrome: Special Reference to Premenopausal Women

It has been proposed that hyperinsulinemia may not constitute a cardiovascular risk in women, and that the metabolic risk profile is less apparent in women than in men. In two different studies, we have assessed the interrelationship between classical coronary risk factors in women with untreated essential hypertension and looked for possible hypertensive-normotensive differences. Hypertensive women (HT1, 156 +/- 2/98 +/- 1 mm Hg, n = 18) in study I turned out to be overweight and had nearly three times higher fasting serum insulin levels than the normotensive control subjects (NT1, 118 +/- 3/77 +/- 2 mm Hg, n = 9). HT1 women with a body mass index (BMI) above 25 kg/m2 had significant higher insulin levels than HT1 women with a BMI less than 25 kg/m2, and when adjusting for BMI the hypertensive-normotensive difference in insulin levels was lost. In HT1 women, the serum insulin level correlated positively to the BMI and triglycerides. In study II, insulin was positively associated with the systolic blood pressure in HTII women (150 +/- 3/99 +/- 1 mm Hg, n = 29), and a negative correlation appeared between the glucose/insulin ratio and the systolic as well as diastolic blood pressure. No difference was observed in BMI and insulin between HTII and NTII women (121 +/- 3/79 +/- 1 mm Hg, n = 18). In HTII women, plasminogen activator inhibitor (PAI-1) levels were higher and the euglobulin clot lysis time prolonged compared to NTII women. PAI-1 was positively correlated to insulin and triglycerides and negatively to high-density lipoprotein (HDL) cholesterol in HTII women. Strong associations between potential cardiovascular risk factors seem to be present even in untreated women with mild hypertension, with insulin being correlated to hypertension, BMI, fibrinolytic activity, triglycerides, and HDL cholesterol.

Hyperinsulinemia and Stromal Luteinization of the Ovaries in Postmenopausal Women With Endometrial Cancer*

Ovarian secretion of testosterone and androstenedione is increased in postmenopausal women with endometrial cancer, and insulin stimulates ovarian stromal androgen synthesis in vitro. We undertook this study to investigate whether women with endometrial cancer have increased serum immunoreactive insulin levels. Ten postmenopausal women with endometrial carcinoma and 10 postmenopausal women without cancer who matched the cancer patients in age, years since menopause, and percentage of ideal body weight were studied. The women with endometrial cancer had significantly higher fasting serum insulin levels than the normal women [mean, 187 +/- 26 (+/- SE) vs. 55 +/- 11 pmol/L; P less than 0.01]. The cancer patients had significantly higher insulin responses after glucose administration than normal women (sum of 1, 2, and 3 h postglucose values, 5545 +/- 1526 vs. 1444 +/- 156 pmol/L; P less than 0.02), even though their glucose responses were similar. Nests of luteinized cells, which were positive for testosterone by immunoperoxidase staining, were found in the ovarian stroma of 8 of the women with endometrial cancer, but in only 1 of those without cancer (P less than 0.01). Specific high affinity insulin receptors were demonstrable in the stroma of the postmenopausal ovaries. These results suggest that the frequency of stromal luteinization is increased in women with endometrial cancer and that insulin may play a role in the pathogenesis of this luteinization.

Pathophysiological interrelations of obesity, impaired glucose tolerance, and arterial hypertension

There is a large amount of epidemiological and clinical evidence for associations among obesity, impaired glucose tolerance, and arterial hypertension; nevertheless, the pathophysiological mechanisms underlying these associations have not yet been elucidated. In this article, some working hypotheses are discussed, and original data are presented from two studies focusing on these pathophysiological interrelations. A case-control study of obese normotensive and hypertensive patients, matched for sex, age, and degree of overweight, has shown that obese patients with associated arterial hypertension have higher fasting serum insulin levels and reduced glucose tolerance compared with their normotensive peers. A second study compared subjects with impaired glucose tolerance with a control group of clinically healthy individuals of comparable sex, age, and body mass index, and it revealed that impaired glucose tolerance is associated with significantly higher blood pressure levels, independent of body weight. The results of the two studies together suggest that the association between hypertension and impaired glucose tolerance is independent of overweight; they also give some support to the hypothesis that hyperinsulinemia may contribute to the development of high blood pressure in obese patients.

Comparison of Feeding Unrefined and Refined Starch Diets on Intestinal Upake and Hepatic Lipogenic Enzymes in the Rat

The rates of intestinal uptake of dietary sugars and amino acids, and changes in serum insulin and hepatic lipogenic enzyme responses were determined in male Wistar rats fed either an unrefined starch (stock) diet or a 65% readily digestible refined starch (corn) or a poorly digestible refined starch (potato) diet. At 45 days of age, rats fed the corn starch diet had 30% to 50% higher fasting serum insulin levels than did rats fed the stock or potato starch diets; however, the differences were not statistically significant. After an average of 9 weeks of being fed the diets, the intestinal uptake of glucose, α-methylglucose and fructose, and the response of hepatic malic enzyme and glucose-6-phosphate dehydrogenase were significantly greater in rats fed the corn starch diet than in rats fed the stock diet, whereas the effect was opposite with leucine and galactose uptake. The intestinal uptake of sugars and amino acids, and hepatic enzyme responses were often similar in rats fed the stock or potato starch diets. Rats fed the potato starch diet had smaller livers than did rats fed the corn starch diet. The livers of rats fed the corn starch or potato starch diets contained less soluble protein than did the livers of rats fed the stock diet. Feeding of the potato starch diet resulted in an abnormally enlarged and bloated gastrointestinal tract and in constrictions of the small intestine which appeared to obstruct the flow of intestinal contents.

Insulin Sensitivity and Adipose Tissue Weight of Rats Fed Starch or Sucrose Diets Ad Libitum or in Meals

The deposition of edidymal and perirenal fat, serum insulin levels, and insulin sensitivity of epididymal fat, expressed as the insulin-stimulated production of CO2 from glucose, were determined in Wistar rats fed diets containing either 54% starch or sucrose ad libitum or pair-fed in meals. Regardless of the pattern of feeding, sucrose-fed rats deposited more adipose tissue per 100 g body weight and exhibited less insulin sensitivity than did starch-fed rats. Significant differences in adipose tissue weights were not always accompanied by significant differences in body weights. Meal-fed rats deposited less adipose tissue and showed a greater insulin sensitivity than did ad libitum rats fed the same carbohydrate. However, when changes in feeding pattern negated the difference in adipose weights there was no difference in the insulin sensitivity of the meal-fed and ad libitum-fed rats. Rats consuming the sucrose diet generally exhibited significantly higher fasting serum insulin levels than did rats consuming the starch diet. The serum insulin values tended to be higher in the ad libitum-fpididymal tissue from the meal-fed and starch-fed rats tended to be greater than that of the sucrose-fed or ad libitum-fed rats, respectively, suggesting differences in adipocyte composition. Since obesity, insulin insensitivity, and hyperinsulinism are associated with an impairment of glucose tolerance, the observed metabolic effects of dietary sucrose are considered to be undesirable.

Serum and urine insulin in late pregnancy and in a few pregnant latent diabetics.

SUMMARY As measured both by immunoassay and bioassay during a glucose tolerance test (50 g.) on ten subjects in the third trimester of pregnancy, the serum insulin levels fasting, 1 and 2 hr. after glucose were raised at least threefold compared with the levels in 23 non-pregnant women. The renal clearance of immunoassayable insulin was lower than that in the non-pregnant state (the mean in the pregnant subjects was 0·18 ml./min. compared with 0·45 ml./min. in the normal non-pregnant subjects). In the same subjects the mean serum non-suppressible insulin-like activity, which is unaltered by oral glucose, was 1·5 times higher than the non-pregnant mean level, but this difference was not significant. Four pregnant latent diabetics, tested similarly in the latter part of pregnancy, showed even higher fasting serum insulin levels than the normal pregnant subjects, but a lessened response to the same glucose load.