Phase Of Insulin Secretion Research Articles

Impaired incretin secretion and pancreatic dysfunction with older age and diabetes

ObjectiveTo estimate the impact of aging and diabetes on insulin sensitivity, beta-cell function, adipocytokines, and incretin production. MethodsHyperglycemic clamps, arginine tests and meal tolerance tests were performed in 50 non-obese subjects to measure insulin sensitivity (IS) and insulin secretion as well as plasma levels of glucagon, GLP-1 and GIP. Patients with diabetes and healthy control subjects were divided into the following groups: middle-aged type 2 diabetes (MA-DM), aged Type 2 diabetes (A-DM) and middle-aged or aged subjects with normal glucose tolerance (MA-NGT or A-NGT). ResultsIS, as determined by the homeostasis model assessment, glucose infusion rate, and oral glucose insulin sensitivity, was reduced in the aged and DM groups compared with MA-NGT, but it was similar in the MA-DM and A-DM groups. Insulinogenic index, first and second phase insulin secretion and the disposition indices, but not insulin response to arginine, were reduced in the aged and DM groups. Postprandial glucagon production was higher in MA-DM compared to MA-NGT. Whereas the GLP-1 production was reduced in A-DM, no differences between groups were observed in GIP production. ConclusionsIn non-obese subjects, diabetes and aging impair insulin sensitivity. Insulin production is reduced by aging, and diabetes exacerbates this condition. Aging associated defects superimposed diabetic physiopathology, particularly regarding GLP-1 production. On the other hand, the glucose-independent secretion of insulin was preserved. Knowledge of the complex relationship between aging and diabetes could support the development of physiopathological and pharmacological based therapies.

Black carrots fermented with Aspergillus oryzae improves cognitive function and insulin resistance in β‐amyloid‐infused diabetic rats (829.4)

We investigated whether the extracts of black carrot (BC) and BC fermented with Lactobacillus plantarum (BCLP) and Aspergillus oryzae (BCAO) can protect against cognitive dysfunction and glucose dysregulation in rats with Alzheimer’s disease and type 2 diabetes. Partial pancreatectomy and ICV β‐amyloid (25‐35) infusion into the CA1 region were fed either control diet (CON), 3% BC, BCAO, or BCLP in a high fat diet for 8 weeks. BCAO increased the contents of total anthocyanins compared to the BC. BC mainly contained cyanidin glycosides whereas after fermentation, the contents of peonidin derivatives increased in the ascending order of BCLP<BCAO. BCAO markedly decreased β‐amyloid deposition and improved hippocampal insulin signaling (pAkt◊pGSK◊pTau) in AD rats. Cognitive function was markedly impaired in AD rats and the cognitive dysfunction was prevented in an ascending order of CON<BC and BCLP<BCAO. BCAO blocked the decrease of whole body glucose infusion rates and the increase of hepatic glucose output at hyperinsulinemic state in AD rats. Interestingly, second phase insulin secretion during hyperglycemic clamp was rampantly increased in AD rats with remarkable decreased β‐cell mass. The BCAO treatment corrected the impaired insulin secretion and decreased β‐cell mass in AD rats. In conclusions, BCAO prevented their impairment of cognitive and glucose homoeostasis in AD diabetic rats as much as Non‐AD rats.

Quantifying Insulin Sensitivity and Entero-Insular Responsiveness to Hyper- and Hypoglycemia in Ferrets

Ferrets are an important emerging model of cystic fibrosis related diabetes. However, there is little documented experience in the use of advanced techniques to quantify aspects of diabetes pathophysiology in the ferret. Glycemic clamps are the gold standard technique to assess both insulin sensitivity and insulin secretion in humans and animal models of diabetes. We therefore sought to develop techniques for glycemic clamps in ferrets. To assess insulin sensitivity, we performed euglycemic hyperinsulinemic clamps in 5–6 week old ferrets in the anesthetized and conscious states. To assess insulin secretion, we performed hyperglycemic clamps in conscious ferrets. To evaluate responsiveness of ferret islet and entero-insular hormones to low glucose, a portion of the hyperglycemic clamps were followed by a hypoglycemic clamp. The euglycemic hyperinsulinemic clamps demonstrated insulin responsiveness in ferrets similar to that previously observed in humans and rats. The anesthetic isoflurane induced marked insulin resistance, whereas lipid emulsion induced mild insulin resistance. In conscious ferrets, glucose appearance was largely suppressed at 4 mU/kg/min insulin infusion, whereas glucose disposal was progressively increased at 4 and 20 mU/kg/min insulin. Hyperglycemic clamp induced first phase insulin secretion. Hypoglycemia induced a rapid diminishment of insulin, as well as a rise in glucagon and pancreatic polypeptide levels. The incretins GLP-1 and GIP were affected minimally by hyperglycemic and hypoglycemic clamp. These techniques will prove useful in better defining the pathophysiology in ferrets with cystic fibrosis related diabetes.

The Incretin Response After Successful Islet Transplantation

The Incretin Response After Successful Islet Transplantation

Preliminary Examination of Olanzapine and Diet Interactions On Metabolism in a Female Macaque.

Clinical data suggest that atypical antipsychotics such as olanzapine (OLZ) induce significant metabolic changes that are serious side effects of their primary use. Since controlled human studies are problematic and rodent data may be poorly translatable, we have initiated development of a macaque model of OLZ-induced metabolic disease. In this preliminary feasibility study, we examined some metabolic effects of OLZ in a female macaque in the context of a standard low-calorie/fat monkey chow diet followed by a high-fat/sugar Western-style diet (WSD). A female Japanese macaque was administered OLZ (1.25 mg/day) for 6 months, with dietary changes at 2-month intervals as follows: OLZ+Restricted chow, OLZ+Unrestricted chow, OLZ+WSD, and placebo+WSD. Weight was assessed weekly. Glucose tolerance tests (GTT) and Dexascans were performed at baseline and every 2 months. Omental (OM) and subcutaneous (SQ) adipose tissue biopsies were obtained at baseline, after OLZ+Unrestricted chow and after OLZ+WSD to evaluate adipocyte size, lipolysis and insulin-stimulated free fatty acid uptake (FFA). A separate trial was conducted on 2 monkeys with 5 days of OLZ- or no-treatment followed by RT-PCR on rostral and medial basal hypothalamus. Weight increased on OLZ+Restricted chow and stabilized on OLZ+Unrestricted chow. OLZ+WSD did not significantly change the weight plateau. Weight declined upon withdrawal of OLZ with continued WSD. Body fat increased from 14% at baseline to 22%, 30%, 28% and 19% at 2, 4, 6 and 8 mo, respectively, indicating that body fat was elevated on OLZ regardless of diet and declined upon OLZ removal. Glucose tolerance and the insulin response during GTT were normal with OLZ+Restricted chow or OLZ+Unrestricted chow. Addition of WSD with OLZ impaired glucose clearance during GTT. Insulin remained in the normal range, but first phase insulin secretion was reduced. After removal of OLZ, but continued WSD, glucose clearance returned to normal, but this was associated with hyperinsulinemia. Adipocyte diameter was increased in OM and SQ fat by OLZ+chow and OLZ+WSD to a similar extent. (p<0.01, 2-way ANOVA). In OM, isoproterenol-stimulated lipolysis occurred at baseline. In both depots, isoproterenol-stimulated lipolysis occurred with OLZ+chow, but it was significantly blunted by addition of WSD (ANOVA p<0.0001; posthoc p<0.05). Insulin increased FFA uptake at baseline. OLZ +chow or OLZ+WSD increased basal FFA uptake and insulin-induced FFA uptake was blunted in both depots (posthoc p<0.05). There was a marked decrease in POMC gene expression, and increased AgRP and NPY expression in the hypothalamus. There was also a clear increase in serotonin (5HT) 2C, melanocortin (MCR4), and Leptin (LepR) receptor gene expression. These data support the hypotheses that OLZ acts on peripheral tissues as well as in the CNS; that changes in hypothalamic gene expression occur very rapidly and precede increased fat accumulation; that adipose tissue exhibits insulin resistance prior to alterations in GTT; that addition of WSD to OLZ precipitates hyperglycemia without an obvious insulin response; and that removal of OLZ and continued WSD resulted in normalized glucose clearance and elevated insulin. These data suggest complex and early responses to OLZ that may be exacerbated by WSD.

Lipoproteins and β-Cell Functions: From Basic to Clinical Data.

Lipoproteins and β-Cell Functions: From Basic to Clinical Data.

Characteristics of Glucose Metabolism in Nordic and South Asian Subjects with Type 2 Diabetes

BackgroundInsulin resistance and type 2 diabetes are more prevalent in people of South Asian ethnicity than in people of Western European origin. To investigate the source of these differences, we compared insulin sensitivity, insulin secretion, glucose and lipid metabolism in South Asian and Nordic subjects with type 2 diabetes.MethodsForty-three Nordic and 19 South Asian subjects with type 2 diabetes were examined with intra-venous glucose tolerance test, euglycemic clamp including measurement of endogenous glucose production, indirect calorimetry measuring glucose and lipid oxidation, and dual x-ray absorptiometry measuring body composition.ResultsDespite younger mean ± SD age (49.7±9.4 vs 58.3±8.3 years, p = 0.001), subjects of South Asian ethnicity had the same diabetes duration (9.3±5.5 vs 9.6±7.0 years, p = 0.86), significantly higher median [inter-quartile range] HbA1c (8.5 [1.6] vs 7.3 [1.6] %, p = 0.024) and lower BMI (28.7±4.0 vs 33.2±4.7 kg/m2, p<0.001). The South Asian group exhibited significantly higher basal endogenous glucose production (19.1 [9.1] vs 14.4 [6.8] µmol/kgFFM⋅min, p = 0.003). There were no significant differences between the groups in total glucose disposal (39.1±20.4 vs 39.2±17.6 µmol/kgFFM⋅min, p = 0.99) or first phase insulin secretion (AUC0–8 min: 220 [302] vs 124 [275] pM, p = 0.35). In South Asian subjects there was a tendency towards positive correlations between endogenous glucose production and resting and clamp energy expenditure.ConclusionsSubjects of South Asian ethnicity with type 2 diabetes, despite being younger and leaner, had higher basal endogenous glucose production, indicating higher hepatic insulin resistance, and a trend towards higher use of carbohydrates as fasting energy substrate compared to Nordic subjects. These findings may contribute to the understanding of the observed differences in prevalence of type 2 diabetes between the ethnic groups.

A possible role of transglutaminase 2 in the nucleus of INS-1E and of cells of human pancreatic islets

Transglutaminase 2 (TG2) is a multifunctional protein with Ca2 +-dependent transamidating and G protein activity. Previously we reported that the role of TG2 in insulin secretion may involve cytoplasmic actin remodeling and a regulative action on other proteins during granule movement. The aim of this study was to gain a better insight into the role of TG2 transamidating activity in mitochondria and in the nucleus of INS-1E rat insulinoma cell line (INS-1E) during insulin secretion. To this end we labeled INS-1E with an artificial donor (biotinylated peptide), in basal condition and after stimulus with glucose for 2, 5, and 8 min. Biotinylated proteins of the nuclear/mitochondrial-enriched fraction were analyzed using two-dimensional electrophoresis and mass spectrometry. Many mitochondrial proteins involved in Ca2 + homeostasis (e.g. voltage-dependent anion-selective channel protein, prohibitin and different ATP synthase subunits) and many nuclear proteins involved in gene regulation (e.g. histone H3, barrier to autointegration factor and various heterogeneous nuclear ribonucleoprotein) were identified among a number of transamidating substrates of TG2 in INS-1E. The combined results provide evidence that a temporal link exists between glucose-stimulation, first phase insulin secretion and the action of TG on histone H3 both in INS-1E and human pancreatic islets.Biological significanceResearch into the role of transglutaminase 2 during insulin secretion in INS-1E rat insulinoma cellular model is depicting a complex role for this enzyme. Transglutaminase 2 acts in the different INS-1E compartments in the same way: catalyzing a post-translational modification event of its substrates. In this work we identify some mitochondrial and nuclear substrates of INS-1E during first phase insulin secretion. The finding that TG2 interacts with nuclear proteins that include BAF and histone H3 immediately after (2–5 min) glucose stimulus of INS-1E suggests that TG2 may be involved not only in insulin secretion, as suggested by our previous studies in cytoplasmic INS-1E fraction, but also in the regulation of glucose-induced gene transcription.

Efficacy and safety of nateglinide plus vildagliptin combination therapy compared with switching to vildagliptin in type 2 diabetes patients inadequately controlled with nateglinide.

To investigate the efficacy and safety of vildagliptin, a potent dipeptidyl peptidase-4 inhibitor, as add-on to nateglinide, compared with switching to vildagliptin in Japanese type2 diabetes patients poorly controlled with nateglinide. A total of 40 patients inadequately controlled with nateglinide were randomized to the switching group (n=20, switching from nateglinide to vildagliptin) or combination group (n=20, nateglinide plus vildagliptin). A meal tolerance test was carried out at weeks 0 and 24. The mean changes in glycated hemoglobin from baseline to week 24 were -1.2±0.3% and -0.3±0.5% in patients of the combination and switching groups, respectively, and the difference between the groups was statistically significant (P<0.001). The mean changes in area under the curve of glucose from 0 to 180min (AUC0-180min) from baseline to week 24 was -361±271.3mmol·min/L in patients of the combination group compared with 141±241.9mmol·min/L in those of the switching group (P<0.001). The incidence of hypoglycemic events was low (three in the combination group), and none of the patients developed severe hypoglycemia. Although the addition of vildagliptin to nateglinide did not significantly increase insulin secretion relative to glucose elevation (ISG) after meal load (ISG0-180min: AUC0-180min insulin/AUC0-180min glucose) in comparison with that in baseline, the mean ISG0-30min 24weeks after addition of vildagliptin to nateglinide was significantly higher than that at baseline. In contrast, switching from nateglinide to vildagliptin reduced the mean ISG0-180min, relative to baseline. The combination therapy of vildagliptin and nateglinide is effective and safe in Japanese type2 diabetes, and the improved glycemic control is as a result of augmentation of nateglinide-induced early phase insulin secretion. This trial was registered with UMIN (no. ID000004010).

Serum retinol binding protein 4 is negatively related to beta cell function in Chinese women with non-alcoholic fatty liver disease: a cross-sectional study

BackgroundTo observe the relationship between serum retinol binding protein 4(RBP4) and β cell function in Chinese subjects with non-alcoholic fatty liver disease (NAFLD) and without known diabetes.Methods106 patients diagnosed as fatty liver by ultrasonography (M/F: 61/45; aged 47.44 ± 14.16 years) were enrolled in our current cross-sectional study. Subjects with known diabetes, chronic virus hepatitis and excessive alcohol consumption were excluded. Serum RBP4 was detected by ELISA and validated by quantitative Western blotting. β cell function were assessed by HOMA in all subjects and by hyperglycemic clamp in 17 normal glucose tolerance subjects (M = 6, F = 11).ResultsThe levels of serum RBP4 in men were higher than that in women (55.96 ± 11.14 vs 45.87 ± 10.31 μg/ml, p < 0.001). Pearson’s correlation analysis demonstrated that in women, serum RBP4 levels were significantly associated with fasting blood glucose (FBG), HOMA-β, and increment of first phase insulin secretion (1PH), but not associated with age, BMI, waist circumference, WHR, systolic (SBP) and diastolic blood pressure (DBP), TC, TG, HDL-c, LDL-c, 2 h blood glucose, HOMA-IR, ALT, AST, γ-GT, hepatic fat content (HFC), and insulin sensitivity index (ISI). However, in men, serum RBP4 levels were significantly associated with HDL-c, ALT, AST, but not associated with any other parameters as mentioned above. A stepwise multiple linear regression analysis demonstrated that in women, HOMA-IR and RBP4 were significantly associated with HOMA-β, while in men, HOMA-IR and BMI were significantly variables associated with HOMA-β.ConclusionsSerum RBP4, secreted mainly by liver and adipose tissue, may involve in the pathogenesis of β cell dysfunction in Chinese women patients with NAFLD.

Actin Dynamics Regulated by the Balance of Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) and Cofilin Activities Determines the Biphasic Response of Glucose-induced Insulin Secretion

Actin dynamics in pancreatic β-cells is involved in insulin secretion. However, the molecular mechanisms of the regulation of actin dynamics by intracellular signals in pancreatic β-cells and its role in phasic insulin secretion are largely unknown. In this study, we elucidate the regulation of actin dynamics by neuronal Wiskott-Aldrich syndrome protein (N-WASP) and cofilin in pancreatic β-cells and demonstrate its role in glucose-induced insulin secretion (GIIS). N-WASP, which promotes actin polymerization through activation of the actin nucleation factor Arp2/3 complex, was found to be activated by glucose stimulation in insulin-secreting clonal pancreatic β-cells (MIN6-K8 β-cells). Introduction of a dominant-negative mutant of N-WASP, which lacks G-actin and Arp2/3 complex-binding region VCA, into MIN6-K8 β-cells or knockdown of N-WASP suppressed GIIS, especially the second phase. We also found that cofilin, which severs F-actin in its dephosphorylated (active) form, is converted to the phosphorylated (inactive) form by glucose stimulation in MIN6-K8 β-cells, thereby promoting F-actin remodeling. In addition, the dominant-negative mutant of cofilin, which inhibits activation of endogenous cofilin, or knockdown of cofilin reduced the second phase of GIIS. However, the first phase of GIIS occurs in the G-actin predominant state, in which cofilin activity predominates over N-WASP activity. Thus, actin dynamics regulated by the balance of N-WASP and cofilin activities determines the biphasic response of GIIS.

Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects

It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p < 0.05) and lower 2-h glucose concentrations during OGTT (r = -0.31; p < 0.05). In addition, fasting (r = -0.36; p < 0.05) and 2-h glucose concentrations were negatively related to circulating levels of soluble receptor for AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.

Cephalic phase insulin secretion is KATP channel independent

Glucose-induced insulin secretion from pancreatic β-cells critically depends on the activity of ATP-sensitive K⁺ channels (KATP channel). We previously generated mice lacking Kir6.2, the pore subunit of the β-cell KATP channel (Kir6.2(-/-)), that show almost no insulin secretion in response to glucose in vitro. In this study, we compared insulin secretion by voluntary feeding (self-motivated, oral nutrient ingestion) and by forced feeding (intra-gastric nutrient injection via gavage) in wild-type (Kir6.2(+/+) and Kir6.2(-/-) mice. Under ad libitum feeding or during voluntary feeding of standard chow, blood glucose levels and plasma insulin levels were similar in Kir6.2(+/+) and Kir6.2(-/-) mice. By voluntary feeding of carbohydrate alone, insulin secretion was induced significantly in Kir6.2(-/-) mice but was markedly attenuated compared with that in Kir6.2(+/+) mice. On forced feeding of standard chow or carbohydrate alone, the insulin secretory response was markedly impaired or completely absent in Kir6.2(-/-) mice. Pretreatment with a muscarine receptor antagonist, atropine methyl nitrate, which does not cross the blood-brain barrier, almost completely blocked insulin secretion induced by voluntary feeding of standard chow or carbohydrate in Kir6.2(-/-) mice. Substantial glucose-induced insulin secretion was induced in the pancreas perfusion study of Kir6.2(-/-) mice only in the presence of carbamylcholine. These results suggest that a KATP channel-independent mechanism mediated by the vagal nerve plays a critical role in insulin secretion in response to nutrients in vivo.

Beta-cell function and insulin sensitivity at various degrees of glucose tolerance in Chinese subjects

AimsThe aim of this study was to evaluate the relative importance of insulin sensitivity (SI), and the first (1st ISEC) and second phase insulin secretion (2nd ISEC) in the development of type 2 diabetes (T2D) in Chinese subjects. MethodsA total of 96 subjects, including 19 with normal fasting glucose, 21 with pre-diabetes, and 56 with T2D were enrolled. Subjects underwent a modified low dose graded glucose infusion (M-LDGGI; a simplified version of Polonsky's method) and frequently sampled intravenous glucose tolerance test. The results were interpreted as the slope of the changes of plasma insulin against the glucose levels. By observing the respective percentage reduction, the deterioration rate of each parameter was compared. ResultsAs fasting plasma glucose (FPG) levels increased, SI decreased mildly and non-significantly, while the 1st and 2nd ISECs decreased more dramatically and significantly. More importantly, the decrease of the 1st ISEC from baseline was greater than that of the 2nd ISEC. ConclusionsSince the 1st ISEC decreased the most with increasing FPG levels, it is concluded that the 1st ISEC is the key trigger of T2D development. On the contrary, the 2nd ISEC remained more stable across increasing FPG levels. This latter finding may explain the effectiveness of insulin secretagogues during the early stage of T2D. The results of this study can be helpful in the development of interventions aimed at stopping the progression and/or treating T2D in Chinese populations.

Insulin resistance and beta-cell function in different ethnic groups in Kenya: the role of abdominal fat distribution

Little is known about the pathophysiology of diabetes in Africans. Thus, we assessed whether insulin resistance and beta-cell function differed by ethnicity in Kenya and whether differences were modified by abdominal fat distribution. A cross-sectional study in 1,087 rural Luo (n = 361), Kamba (n = 378), and Maasai (n = 348) was conducted. All participants had a standard 75-g oral glucose tolerance test (OGTT). Venous blood samples were collected at 0, 30, and 120 min. Serum insulin was analysed at 0 and 30 min. From the OGTT, we assessed the homoeostasis model assessment of insulin resistance by computer model, early phase insulin secretion, and disposition index (DI) dividing insulin secretion by insulin resistance. Abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) thickness were carried out by ultrasonography. Linear regression analyses were done to assess ethnic differences in insulin indices. The Maasai had 32 and 17% higher insulin resistance than the Luo and Kamba, respectively (p < 0.001). Early phase insulin secretion was 16% higher in the Maasai compared to the Luo (p < 0.001). DI was 12% (p = 0.002) and 10% (p = 0.015) lower in the Maasai compared to the Luo and Kamba, respectively. Adjustments of SAT (range 0.1-7.1 cm) and VAT (range 1.5-14.2 cm) largely explained these inter-group differences with the Maasai having the highest combined abdominal fat accumulation. The Maasai had the highest insulin resistance and secretion, but the lowest relative beta-cell function compared to the Luo and Kamba. These differences were primarily explained by abdominal fat distribution.

First phase insulin secretion is impaired by aldosterone excess in primary aldosteronism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Impact of Low Dose Prenatal Ethanol Exposure on Glucose Homeostasis in Sprague-Dawley Rats Aged up to Eight Months

Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring’s health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.

The effect of chromium on inflammatory markers, 1st and 2nd phase insulin secretion in type 2 diabetes

Impaired insulin sensitivity (SI) and β-cell function are the two main causes of type 2 diabetes (T2D) and are related to low-grade inflammation status. Trivalent chromium has shown to improve SI in our previous study. This might be due to the ability of decreasing interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) shown in animal studies. In the current study, we measured SI, β-cell function, and plasma levels of IL-6 and TNF-α after treatment of chromium chloride (GaCr) in T2D. Sixty-six patients were randomly assigned to the 20 g of GaCr milk powder studying group or the milk powder placebo group. Oral glucose tolerance test was performed before and after the treatment. The SI and the β-cell function were measured as well. The SI was significantly improved. At the same time, the static insulin responsivity index (Φs) was significantly higher after the treatment (p = 0.003). On the other hand, the dynamic insulin responsivity index (Φd) remained unchanged. Interestingly, a significant decrease in the IL-6 level after the treatment (p = 0.015) was noted. Although there was a trend of decreasing in TNF-α, it was not statistically significant. Finally, there was no significant correlation between the δ-IL-6, SI, and Φd after GaCr treatment. In conclusion, other than the improvement of SI, GaCr could also improve the second phase of insulin responsivity (Φs) and IL-6. However, δ-IL-6 was correlated with neither δ-SI nor δ-Φs which indicated that the improvement of SI and Φs might involve mechanisms other than lower inflammatory effect.

First phase insulin secretion is impaired by aldosterone excess in primary aldosteronism

First phase insulin secretion is impaired by aldosterone excess in primary aldosteronism

Insulin secretion is increased in non‐diabetic subjects with fasting hypertriglyceridaemia

The elevation of triglycerides is strongly linked with insulin resistance, but it has not been evaluated in relationship to insulin secretion. The aim of this study was to determine whether hypertriglyceridaemia is associated with abnormal insulin secretion. A cross-sectional study was carried out. Eligible subjects, apparently healthy men and non-pregnant women aged 20-65 years were recruited. According to the triglyceride levels, subjects were allocated in the groups with hypertriglyceridaemia and normotriglyceridaemia. Hypertriglyceridaemia was defined by serum triglyceride levels ≥150 mg/dL. Insulin secretion was evaluated by the first phase of insulin secretion (1st PIS) and the second phase of insulin secretion (2nd PIS). A regression linear analysis was performed to evaluate the association between hypertriglyceridaemia (independent variable) and the first and second phase insulin secretion (dependent variables). A total of 247 apparently healthy subjects were enrolled; 113 (45.7%) with hypertriglyceridaemia and 134 (54.3%) in the control group. The simple regression linear analysis showed a significant association between hypertriglyceridaemia and the 1st PIS [B = 207.0; 95% confidence interval (CI) 33.5-380.5, p = 0.02] and the 2nd PIS (B = 48.7; 95% CI 9.2-88.2, p = 0.01). A multiple regression linear analysis adjusted by age, sex, body mass index and waist circumference was performed showing that fasting hypertriglyceridaemia remained significantly associated with the 1st PIS (B = 184.3; 95% CI 13.0-355.7, p = 0.03) and the 2nd PIS (B = 43.1; 95% CI 4.2-81.9, p = 0.03). The results of this study show that hypertriglyceridaemia is associated with the increase of the 1st PIS and the 2nd PIS in apparently healthy subjects.