We previously reported that brain-derived neurotrophic factor (BDNF) regulates both food intake and blood glucose metabolism in rodent obese diabetic models such as C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice. Furthermore, C-peptide stimulates glucose transport in human muscle strips of nondiabetic and diabetic subjects (3). Euglycemic hyperinsulinemic (80 mU/m(2) ) clamp with -3H-glucose and muscle biopsies were performed. Glucagon was not replaced, thus allowing assessment of the direct effect of insulinopenia at the liver independent of the potentiation of glucagon action. In humans, high-fat diets, independent of fatty acid profile, have been reported to result in decreased insulin sensitivity. The GSK-3 inhibitor effect, like that of insulin, was on the activation state (fractional velocity [FV]) of GS. The diabetic patients showed significantly lower rMRGlu-rCBF values in all regions than controls, whereas non-diabetic patients did not.
Thus, IMCL-T reflects insulin sensitivity, whereas IMCL-S relates to obesity. © 2015 by the American Diabetes Association. The risk of depressive symptoms associated with PDM was attenuated to be non-significant after pooling RRs that were adjusted for diabetes-related comorbidities. CD). To date he has displayed poor diabetic control and high ferritin. Skeletal muscle insulin resistance is a key feature of the metabolic syndrome and predisposes to type 2 diabetes and premature cardiovascular complications (8). Although lifestyle (9), obesity, and increased lipid supply play an important role in this disease (8,10), the hierarchy of events is still unclear.
It was postulated that muscle fat content could contribute to insulin resistance and glucose intolerance (11–19), but only the advent of 1H nuclear magnetic resonance spectroscopy (NMRS) made it possible to quantify and distinguish between extramyocellular and intramyocellular lipid contents (IMCL) (11,14,15,17,18,20–22). Acquisition of data, S.P., M.S., K.S.-S., J.K., H.W., and E.T. The DM-IS group was characterized by an absence of IR, diminished GEZI, and a reduction in AIRg; whereas the DM-IR group was characterized by IR and a reduction in AIRg, but normal GEZI. IMCL were correlated with parameters of glucose tolerance, insulin sensitivity, cardiovascular risk, body fat content, and distribution. Three-hundred seven patients had their OGTT (fasting and 2-h glucose) completed by March 2010, and OGTT-derived data were included in the present analysis. All women ingested an isocaloric diet containing 200 g of carbohydrates/day and refrained from exercise for at least 3 days before the studies. We will purify and identify cellular proteins associated with SIRT1 in beta- cells and investigate the roles of these interactions in regulating glucose metabolism.
Cross-sectional analysis was performed in 39 pGDM women at 4–6 months after delivery. They were recruited from our division’s outpatient service, where they had been seen previously during pregnancy. Dr. During pregnancy, 26 women were treated with diet plus insulin, because blood glucose exceeded 95 mg/dl at fasting and/or 130 mg/dl at 60 min postprandially. (2001) Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. All subjects gave written informed consent for participation in the study, which was approved by the local ethics committee. Patients with previous ketoacidosis and/or β-cell antibodies (GAD, ICA, IA2) were excluded.
The relationship among IMCL, insulin sensitivity, and metabolic parameters was analyzed both in the total pGDM population and for the insulin-sensitive (pGDM-S) and insulin-resistant subgroups (pGDM-R), which were separated by a cutoff value of 2.8 10−4 min−1/(μU/ml) for the insulin sensitivity index (SI). The higher triglyceride levels were probably related to the insulin resistance or unhealthy lifestyles that were more common in the subgroup with suicidal behaviour . The lower 2.5% quantile of the distribution gave an SI of 2.79 10−4 min−1/(μU/ml), which was defined as the cutoff point between normal and impaired (lower) SI. These results indicate that TCF7L2 may be an important mediator of the GLP-1 signaling pathway in the brain, and indicate a central action of TCF7L2 in control of glucose homeostasis. After correction for BMI, differences in waist-to-hip-ratio disappeared, whereas waist circumference remained different (P < 0.01). 38, 985–995 (2006). In contrast, pGDM-R had higher BMI and systolic blood pressure but lower HDL cholesterol. Participating controls did not use any medication except for one person using omeprazol because of gastroesophageal reflux disease and one person using terbutaline because of mite allergy. After correction for lean body mass, i.e., fat-free mass (FFM), the basal metabolic rate was not different between pGDM (30.50 ± 0.33 kJ/kg FFM) and NGT (30.57 ± 0.39 kJ/kg FFM) but lower in pGDM-R (29.35 ± 0.50 kJ/kg FFM) than pGDM-S (31.58 ± 0.42 kJ/kg FFM, P < 0.003) and NGT (P < 0.03). Glucose (time 0–0.5 min: 300 mg/kg BW) and then normal insulin (time 20–25 min: 0.03 IU/kg, Humulin R; Eli Lilly, Indianapolis, IN) were infused intravenously, and venous blood samples were taken in timed intervals (28). Analysis of glucose and insulin concentrations provided indexes for glucose tolerance (KG), insulin sensitivity (SI), and glucose effectiveness (SG), which describe glucose disposal and the insulin effect on glucose disappearance (28). Insulin secretion was assessed from incremental short-term insulin response (ΔAIRG) calculated by averaging insulin concentration above basal from times 3–10 min. The disposition index was calculated as SI times ΔAIRG and gives a measure of the combined effects of insulin secretion and sensitivity on glucose disposal (29). Participants ingested 75 g of glucose solution, and venous blood samples were collected for glucose, insulin, and C-peptide measurements at timed intervals (30). Modeling analysis yielded fasting prehepatic insulin secretion rate and the total amount of insulin per unit volume released during the OGTT in response to increments in glucose concentration (30). Insulin sensitivity from OGTT (OGIS) was derived as glucose clearance (ml · min−1 · m−2) (31). IMCL was measured with localized 1H NMRS (17,20,21) on a 3.0-T/80-cm NMR spectrometer (Medspec; Bruker, Ettlingen, FRG) equipped with a whole-body gradient coil (40 mT/m; Fig. 1). A standard birdcage 1H coil (inner diameter 25 cm) was used in the transmission/reception mode. The STEAM sequence (echo time 20 ms; mixing time 30 ms; relaxation time 6 s; number of scans 32) was complemented by CHESS water suppression and applied on the 1.73-cm3 volume of interest, which was placed in the soleus or tibialis anterior muscles of the subject’s right leg. Spectra were line-broadened and -fitted using the MacNUTS-PPC software (Acorn NMR, Livermore, CA). IMCL was quantified from processed spectra after T2-relaxation correction as a ratio of the intensity of (CH2)n (1.25 ppm) group resonance to the intensity of the water resonance from non-water-suppressed spectra of the same volume of interest (Fig. 1). The T2 relaxation times were of 82 ± 3 ms for IMCL-S and 30 ± 2 ms for water in soleus muscle and 90 ± 6 ms for IMCL-T and 27 ± 1 ms for water in tibialis anterior muscle. The coefficients of variation for 1H NMRS of IMCL, as assessed from three measurements of the lipid content in each muscle in six healthy young subjects, were 0.3% for soleus muscle and 1.3% for tibialis anterior muscle, respectively. Body fat mass (BFM) was assessed from bioimpedance measurements (Akern-RJL Systems, Florence, Italy) as was the basal metabolic rate. For instance, Hughey et al. Resting energy expenditure is expressed per kg BW as well as per kg FFM.