Lecithin Inclusion by α-Cyclodextrin Activates SREBP2 Signaling in the Gut and Ameliorates Postprandial Hyperglycemia

Background: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear. Methods: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice. Results: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr, Hmgcr, Pcsk9, and Srebp2). Conclusions: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.

Striatal DAT availability does not change after supraphysiological glucose loading dose in humans

Brain dopamine neurotransmission is regulated by the dopamine transporter (DAT), which drives reuptake of extracellular dopamine into the presynaptic neurons. We hypothesized that the glucose loading dose would affect the striatal DAT availability. An i.v. bolus injection of 18F-FP-CIT was administered after infusion of low-dose glucose (300 mg/kg), high-dose glucose (600 mg/kg) or placebo (normal saline). The emission data were acquired over 90 min in 23 healthy male subjects. Substantial increases of binding potential (BPNDs) from ventral striatum (VST), caudate nucleus, and putamen were observed after low-dose glucose loading (+26.0, +87.0, and +37.8%) and after high-dose glucose loading (+10.4, +51.9, and +22.0%). BPNDs of the caudate nucleus and putamen showed significant differences (P = 0.0472 and 0.0221) after placebo, low-dose glucose, and high-dose glucose loading. BPNDs in the caudate nucleus and putamen after placebo, low-dose glucose, and high-dose glucose loading were positively intercorrelated with each other. In conclusion, striatal DAT changes after physiological glucose loading, but not after supraphysiological glucose loading in humans. DAT availabilities after placebo, low-dose glucose, high-dose glucose loading were correlated to each other in the caudate nucleus and putamen, but not in the VST. Therefore, sub-regional variability in DAT regulatory mechanisms mediated by insulin may exist in humans.

Clinical and diagnostic features of polycystic ovary syndrome on the background of isulinresistance and hyperandrogenism

Aim of the study: to study the clinicodiagnostic features of polycystic ovarian syndrome (PCOS) against the background of insulin resistance (IR) and hyperandrogenism (HA).Material and methods. We examined 120 women with PCOS and HA, 76 (63.3%) of the total number had IR. The average age of women was 28.54 ± 0.74 (20–44). In women with HA and PCOS against the background of IR, the levels of follicle-stimulating (hFSH), luteinizing (LH), thyrotropic (TТH) hormones were detected, as well as LH/hFSH ratio, prolactin (PRL), estradiol (E2), estrone (E1), total testosterone (T-total), DHEAS, androstenedione (Adione), cortisol (C), 17 hydroxyprogesterone (17-OPG), free triiodothyronine (T3), free thyroxine (T4), SHBG and Anti- Mullerian Hormone (AMH). The levels of carbohydrate metabolism, including glucose, insulin (on an empty stomach), after glucose loading, were determined as well as the HOMA and CARO indices.Results. It was found that according to the Ferriman–Gallwey score, hirsutism was within the range of 16.15 ± 0.34 (11–24) points, hormones — 13.17 ± 0.30 (9–20) points in the examined patients. The indiff erent number was 2.93 ± 0.11 (2–4) points. The average weight of patients was 74.1 ± 1.79 (50–134) kg, height 1.62 ± 0.005 (1.52–1.78) m, Index of Mass Corporal was within 28.56 ± 0.66 (19.5–51.4) kg/m2. In 81.5% of patients with HA and PCOS, absolute sterility was noted on the background of IR. According to hormones studies, there was a statistically signifi cant increase in LH (14.0 ± 0.87 mIU/ml), LH/hFSH (2.39 ± 0.15), TSH (2.83 ± 0.23 mIU/ml), DHEAS (3.32 ± 0.21 pg / ml), 17-OPG (1.0 ± 0.08 ng/ml), Adione (3.94 ± 0.1 ng/ml), T-total (1, 15 ± 0.006 ng/ml), K (125.39 ± 2.86 ng/ml), AMH (7.84 ± 0.36 ng/ml), E1 (153.36 ± 4.56 ng/ml) and decrease in E2 (65.32 ± 2.38 pg/ml), SHBG (36.1 ± 2.0 nmol/l). The study of carbohydrate metabolism and some anthropometric parameters revealed an increase in OB (100.66 ± 1.76 cm), OB / OT (0.86 ± 0.005), glucose and insulin (on an empty stomach) parameters and after glucose loading and HOMA index with a signifi cant decrease in the SAR index. According to the ultrasound data, patients with HA and PCOS against the background of IR revealed a statistically signifi cant decrease in the length and width of the uterus and an increase in the length, thickness, volume of the endometrium, the number of atresic follicles in both ovaries compared to similar data in practically healthy women (p <0.05).

Postloading insulinemia is independently associated with arterial stiffness in young Japanese persons

Associations of arterial stiffness with glucose, insulin, and proinsulin dynamics during the oral glucose tolerance test (OGTT) remain under debate. The aim of this study was to investigate whether plasma glucose (PG), insulin, and proinsulin (Pro) contribute to arterial stiffness, measured by pulse wave velocity (PWV), in young Japanese persons. PG, immunoreactive insulin (IRI), and Pro levels were determined in 1193 young Japanese subjects (<40 years of age) with normal glucose tolerance or nondiabetic hyperglycemia before and at 30, 60, and 120 min during a 75-g OGTT. Participants were divided into two groups according to the median PWV. Background factors, PG, IRI, and Pro levels during the OGTT, and insulin sensitivity (SI) indices in each group were compared. Several multiple regression analysis models were used to evaluate factors contributing to PWV. All IRI and Pro levels before and after glucose loading and the area under the curve (AUC) values for IRI and Pro increased with higher PWV. 1/HOMA-IR and ISI-Matsuda as measures of SI decreased with higher PWV. The IRI AUC and Pro level before glucose loading (Pro0) were independently associated with PWV, in addition to male sex, heart rate, and mean blood pressure. The IRI AUC had a stronger relationship with PWV than Pro0. The IRI AUC had an independent relationship with PWV, whereas both SI indices did not. Postloading insulinemia, but not reduced SI, was independently associated with arterial stiffness in young Japanese persons.

Definition of Norma / Prediabetes Cut-off Point for Fasting Glycaemia on the Basis of Glucose Tolerance Test and HbA1c Interrelationships

Unification of the approach to the diagnosis of prediabetes (PD) is hardly in doubt. The borderline between PD and diabetes is recognized by all, as well as the upper and lower bounds of PD according to the results of glycemia 120 minutes after 75 g glucose loading (GL120). There are still ambiguities regarding glycohemoglobin (HbA1c) and fasting glycemia (FG). For determination of the Norma/PD cut-off point for FG, we analyzed 85 nondiabetic glucose tolerance test results (75.0 glucose; Samples of fasting blood, and 30, 60, 90, 120 minutes after glucose loading) by using correlation and regression analysis. Glycemic values were measured in mg/dl, HbA1c values were measured in %. The fact of identifying the relationship between FG and Gl120 (r=+0.52 [95%CI +0.346, +0.659]; p&lt;0.001), as well as between FG and HbA1c (r=+0.59 [95%CI +0.432, +0.713]; p&lt;0.001) were the basis of this study. As a result of using regression analysis, multiple regression equations were obtained. GL0 =-4.2439 + 0.1927 * GL120 + 15.462 * HbA1c If GL120 is equal to 139 mg/dl (in accordance with all recommendations), and HbA1c is equal to 5.9% (in accordance with the recommendations of NICE, Canadian Diabetes Association, Australian Diabetes Association, et al.), the maximal normal value for FG should be equal to 114 mg/dl. If GL120 is 139 mg/dl and HbA1c is 5.6% (as recommended by the American Diabetes Association), the maximum normal value of FG should be 109 mg/dl. The optimal upper limit of normal carbohydrate metabolism is levels of GL120 equal to 139 mg/dl, HbA1c - equal to 5.6%, and FG - equal to 109 mg/dl. Values above these and below diabetic levels (200 mg/dl, 6.5%, and 126 mg/dl, respectively) can be considered as prediabetes.