Diabetic Volunteers Research Articles

Hyperinsulinaemia Insulin Resistance and Cardiometabolic Risk Profile in Siblings of Type 2 Diabetics

Objective: To compare non-diabetic siblings of Type 2 diabetics for insulin resistance, hyperinsulinaemia, dyslipidemia and biometric indices with non diabetic volunteers with no family history of diabetes. Study Design: Cross sectional analytical study. Place and Duration of Study: A tertiary care teach-ing institution during Dec.2009 to July 2010. Methodology: Siblings of type 2 diabetics above the age of 25 years were matched as closely as possible for age, sex socioeconomic conditions with non diabe-tic volunteers with no family history of diabetes. Both groups were compared for fasting serum insulin, glu-cose, lipid levels and biometric indices using independent t-test. Insulin resistance was calculated by the Quicki (Quantitative insulin check index) method with cutoff at 0.34 on R.O.C analysis. Results: The 106 non diabetic siblings of Type 2 dia-betes mellitus (Group 1) with a mean age of 40.8 ± 12.1 years p value 0.13 were compared to 106 non dia-betic volunteers (Group 2) mean age 43.5 ± 14.2 years. Out of a total of 212 participants 20 (9.4%) subjects had hyperinsulinaemia (mean serum insulin15.69 ± 6.02 µU/L p < 0.001) and insulin resistance (90% sen-sitivity CI 86 to 94, 98.96% specificity CI 97.7 to 100) and all belonged to group 1. A further comparison of the above variables was made within group 1 between 20 (9.4%) insulin resistant siblings and 86 (90.6%) non insulin resistant siblings. The insulin resistant sib-lings showed significant increase in HbA 1 c 7.02% ± 1.5 vs 6.2% ± 1.49 p = 0.008, BMI 30.4 ± 6.4 kg/m 2 vs. 27.1 ± 4.7 kg / m 2 p = 0.01and Serum insulin levels 15.92 ± 6.11 vs. 4.57 ± 2.38 p < 0.001. Conclusion: The study suggests that siblings of dia-betics are a special group who have hyperinsulinemia, insulin resistance and obesity and are at high risk for developing type 2 diabetes. Key words: Hyperinsulinaemia, insulin resistance, BMI, siblings, metabolic syndrome.

Medium- and Short-Term Interventions with Ma-Pi 2 Macrobiotic Diet in Type 2 Diabetic Adults of Bauta, Havana

Background. In Cuba, the Ma-Pi 2 macrobiotic diet has shown positive results in 6-month assays with type 2 diabetic patients. The objective of this study was to assess the influence of this diet at short and medium terms. Methods. Sixty-five type 2 diabetic volunteers were included for dietary intervention, institutionally based for 21 days and followed later at home, until completing 3 months. 54 of them stayed until assay end. Before intervention, and after both assay periods, they were submitted to anthropometric records, body composition analyses and measurements of serum biochemical indicators, glycemic profile in capillary blood, blood pressure, and medication consumption; food intake was evaluated by the 3-day dietary recall. Results. During the intervention, the energy intake was 200 kcal higher at instance of more complex carbohydrates and dietary fiber and despite less fat and protein. Blood pressure and serum biochemical indicators decreased significantly in both periods; the safety nutritional indicators (hemoglobin, serum total proteins, and albumin) showed no variations. The global cardiovascular risk decreased and insulin consumption dropped by 46% and 64%, in both periods, respectively. Conclusions. The Ma-Pi 2 macrobiotic diet was a successful therapy at short term and after 3-month home-based intervention, for type 2 diabetics.

Potential regulatory role of calsequestrin in platelet Ca2+ homeostasis and its association with platelet hyperactivity in diabetes mellitus

Altered Ca(2+) homeostasis contributes significantly to platelet hyperactivity in diabetes mellitus. Calsequestrin (CSQ), as a Ca(2+) buffer protein in the sarcoplasmic reticulum, also regulates the Ca(2+) release process in muscles. We hypothesized that CSQ may be expressed in platelets, but is altered and involved in diabetic platelet Ca(2+) abnormalities and hyperaggregability. CSQ expression in platelets from streptozotocin-induced type 1 diabetes rats, type 2 diabetes volunteers and Goto-Kakizaki rats were analyzed by western blotting and RT-qPCR. Platelet Ca(2+) and aggregation were evaluated with Fura2 and an aggregometer, respectively. Platelets from diabetic patients and rats exhibited increased resting Ca(2+) levels, and hyperactive Ca(2+) and aggregation responses to agonists. This enhanced basal Ca(2+) was largely dependent on intracellular Ca(2+) and insensitive to inositol 1,4,5-trisphosphate receptor (IP(3)R) antagonism. Additionally, the expression of the skeletal CSQ isotype (CSQ-1) was detected in both rat and human platelets, but its levels were significantly lowered in diabetic platelets as compared with normal platelets. Impairment of CSQ by trifluoperazine caused concentration-dependent Ca(2+) release in normal platelets and HEK293 cells. Knocking down CSQ-1 in HEK293 cells resulted in increased leakage of Ca(2+), which was also insensitive to IP(3)R inhibition, and exaggerated Ca(2+) release following carbachol treatment. Downregulation of CSQ-1 in diabetic platelets and impairment of CSQ-1 in normal cells leads to disturbed Ca(2+) release, demonstrating a potential role for CSQ-1 in the regulation of the platelet Ca(2+) release process and a possible causal contribution to diabetic platelet hyperactivity.

Methylene Tetrahydrofolate Reductase Gene Polymorphism and the Risk of Ischemic Stroke in Type 2 Diabetic Egyptian Patients

Background: A common C677T mutation of methylenetetrahydrofolate reductase (MTHFR) gene is reported to be associated with hyperhomocysteinemia a risk for atherosclerotic vascular diseases and ischemic stroke (IS). Aim: To clarify the possible role of the MTHFR 677C>T polymorphism in predisposition to IS and to assess the relationship of allelic variants of MTHFR gene with homocysteine (Hcy) plasma levels and other risk factors of atherosclerosis and IS in type 2 diabetic Egyptians. Subjects: Group I: 40 healthy non diabetic volunteers. Group II: 40 patients with type 2 diabetes mellitus (DM) without IS. Group III: 40 patients with type 2 DM and IS. Methods: Fasting blood samples were collected for research investigations. HPLC technique was used to estimate plasma Hcy levels. Polymerase chain reaction (PCR) assay with restriction fragment length polymorphism (RFLP) were used to examine the MTHFR polymorphism. Results: The frequencies of T allele and TT genotype were significantly higher in group III patients when compared to group I and group II (P T polymorphism is associated with elevated Hcy and uric acid plasma levels which increases the atherogenic risk and the prevalence of IS in type 2 diabetic Egyptian patients.

Effect of acute consumption of strawberry jam on glycaemic status in both non-complicated and type 2 diabetic obese volunteers: a pilot study

The aim of this intervention trial was to evaluate the impact of consumption of two different types of strawberry jam on glycaemic status in 16 non-complicated and 7 type 2 diabetic volunteers, having a body mass index higher than 30 kg/m2 (obesity status) and selected according to the specific criteria. Volunteers consumed a test meal consisting of 30 g of white bread, 50 g of an experimental jam (sweetened with organic apple juice) and 150 ml of whole cow milk; a control jam (sweetened with white beet sugar) was provided within the same test meal with a week gap. For the determination of glucose and insulin levels, venous blood samples were collected after overnight fasting and every 30 min for 3 h after the ingestion of the test meal. Both groups of volunteers had a significantly lower (P < 0.05) increase of glucose and insulin levels at 30 and 60 min after the consumption of the experimental jam with respect to the control one, highlighting the importance of the type of carbohydrates in controlling glycaemic status: indeed, this type of jam, containing mainly fructose, was successful not only for diabetics but also for subjects at risk of developing this pathology, with a severe obesity condition. The consumption of this kind of product could be a strategy to enhance the quality of life in type 2 diabetic people, helping them to follow a dietary regimen including highly accepted food.

Effect of acute consumption of strawberry jam on glycaemic status in both non-complicated and type 2 diabetic obese volunteers: a pilot study

Effect of acute consumption of strawberry jam on glycaemic status in both non-complicated and type 2 diabetic obese volunteers: a pilot study

Glipizide Pharmacokinetics in Healthy and Diabetic Volunteers

Purpose: Disease state may contribute to alteration in drug pharmacokinetics. The purpose of this study was to determine the effect of non-insulin dependent diabetes mellitus (NIDDM) on the pharmacokinetics of glipizide. Methods: An open, single-dose, parallel design was applied to the study. Glipizide tablet (5 mg) was administered to healthy and diabetic human volunteers after over-night fast. Blood samples were collected, centrifuged and the plasma assayed using a sensitive and validated reverse phase high performance liquid chromatography (RP-HPLC) method. Various pharmacokinetic parameters were computed from the data obtained. Results: The AUC 0-� values for healthy and diabetic volunteers was 1878 ± 195 and 1723 ± 138 ng.h/ml, respectively; these values were not significantly different (p > 0.05). The t 1/2 for healthy volunteers was 3.04 ± 0.27 h while that for diabetic subjects was 2.98 ± 0.16 h. Clearance for healthy and diabetic volunteers was 0.59±0.06 and 0.64±0.05 ml/min/kg, respectively. These and other pharmacokinetic parameters assessed were not significantly different between healthy and diabetic volunteers (p > 0.05). Conclusion: Although glipizide showed slightly more rapid clearance from the body of diabetic volunteers than from healthy volunteers, this difference, like those for other pharmacokinetic parameters, was not significant (p > 0.05).

Rhythmic Diurnal Gene Expression in Human Adipose Tissue From Individuals Who Are Lean, Overweight, and Type 2 Diabetic

OBJECTIVEPrevious animal studies suggest a functional relationship between metabolism, type 2 diabetes, and the amplitude of daily rhythms in white adipose tissue (WAT). However, data interpretation is confounded by differences in genetic background and diet or limited sampling points. We have taken the novel approach of analyzing serial human WAT biopsies across a 24-h cycle in controlled laboratory conditions.RESEARCH DESIGN AND METHODSLean (n = 8), overweight/obese (n = 11), or overweight/obese type 2 diabetic (n = 8) volunteers followed a strict sleep–wake and dietary regimen for 1 week prior to the laboratory study. They were then maintained in controlled light–dark conditions in a semirecumbent posture and fed hourly during wake periods. Subcutaneous WAT biopsies were collected every 6 h over 24 h, and gene expression was measured by quantitative PCR.RESULTSLean individuals exhibited significant (P < 0.05) temporal changes of core clock (PER1, PER2, PER3, CRY2, BMAL1, and DBP) and metabolic (REVERBα, RIP140, and PGC1α) genes. The BMAL1 rhythm was in approximate antiphase with the other clock genes. It is noteworthy that there was no significant effect (P > 0.05) of increased body weight or type 2 diabetes on rhythmic gene expression.CONCLUSIONSThe robust nature of these rhythms and their relative phasing indicate that WAT now can be considered as a peripheral tissue suitable for the study of in vivo human rhythms. Comparison of data between subject groups clearly indicates that obesity and type 2 diabetes are not related to the amplitude of rhythmic WAT gene expression in humans maintained under controlled conditions.

Effect of Amla fruit (Emblica officinalis Gaertn.) on blood glucose and lipid profile of normal subjects and type 2 diabetic patients

The present study evaluated the anti-hyperglycemic and lipid-lowering properties of Emblica officinalis Gaertn. fruit in normal and diabetic human volunteers. The results indicated a significant decrease (P < 0.05) in fasting and 2-h post-prandial blood glucose levels on the 21st day in both normal and diabetic subjects receiving 1, 2 or 3 g E. officinalis powder per day as compared with their baseline values. Significant (P < 0.05) decreases were also observed in total cholesterol and triglycerides in both normal and diabetic volunteers on day 21 that were given either 2 or 3 g E. officinalis powder per day. However, diabetic volunteers receiving only 3 g E. officinalis powder exhibited a significant (P < 0.05) decrease in total lipids on day 21. Both normal and diabetic volunteers receiving 2 or 3 g E. officinalis powder significantly (P < 0.05) improved high-density lipoprotein-cholesterol and lowered low-density lipoprotein-cholesterol levels.

NUTRITIONAL VALUE AND GLYCAEMIC INDEX OF KFC AND LOCAL BURGERS IN NORMAL AND DIABETIC HUMAN SUBJECTS

Prevalence of diabetes mellitus has increased all over the world particularly in the developing countries including Pakistan. A study was designed to determine the nutritive value and glycaemic responses of 5 different test and control meals including chapatti + eggs and three varieties of KFC burger (Zinger, Chicken, Sub 60) and local burgers. To determine the nutritive value approximate analysis (CHO, Protein, fat, ash, fibre contents) of 6 different meals were done and to determine the glycaemic responses blood was taken by Finger Prick method and glycaemic responses were noted after 0, 30, 60, 90, 180, 120 minutes for diabetic volunteers on 0, 15, 30, 45, 60, 90, 120 minutes for normal volunteers. It was observed that all the five burgers included in the study possess high glycaemic indices. It is conceivable; therefore, that diabetic patients and obese individuals should not take all these burgers in their daily routine

Noninvasive measurement of plasma glucose from exhaled breath in healthy and type 1 diabetic subjects

Effective management of diabetes mellitus, affecting tens of millions of patients, requires frequent assessment of plasma glucose. Patient compliance for sufficient testing is often reduced by the unpleasantness of current methodologies, which require blood samples and often cause pain and skin callusing. We propose that the analysis of volatile organic compounds (VOCs) in exhaled breath can be used as a novel, alternative, noninvasive means to monitor glycemia in these patients. Seventeen healthy (9 females and 8 males, 28.0 ± 1.0 yr) and eight type 1 diabetic (T1DM) volunteers (5 females and 3 males, 25.8 ± 1.7 yr) were enrolled in a 240-min triphasic intravenous dextrose infusion protocol (baseline, hyperglycemia, euglycemia-hyperinsulinemia). In T1DM patients, insulin was also administered (using differing protocols on 2 repeated visits to separate the effects of insulinemia on breath composition). Exhaled breath and room air samples were collected at 12 time points, and concentrations of ~100 VOCs were determined by gas chromatography and matched with direct plasma glucose measurements. Standard least squares regression was used on several subsets of exhaled gases to generate multilinear models to predict plasma glucose for each subject. Plasma glucose estimates based on two groups of four gases each (cluster A: acetone, methyl nitrate, ethanol, and ethyl benzene; cluster B: 2-pentyl nitrate, propane, methanol, and acetone) displayed very strong correlations with glucose concentrations (0.883 and 0.869 for clusters A and B, respectively) across nearly 300 measurements. Our study demonstrates the feasibility to accurately predict glycemia through exhaled breath analysis over a broad range of clinically relevant concentrations in both healthy and T1DM subjects.

NUTRITIVE VALUE OF CHICKEN PATTY AND FOUR DIFFERENT PIZZAS, AND THEIR GLYCAEMIC INDICES IN NORMAL AND DIABETIC VOLUNTEERS

The study was designed to determine the blood glucose response of six different snakes/meals including chapatti + egg, chicken patty and pizza from three different local bakeries and pizza makers of Faisalabad, Pakistan. The approximate analysis of six different test meals was done for determination of carbohydrates, proteins, fats, ash and fibre contents. A group of 6 normal and 6 diabetic human volunteers were selected and given the test and control meals randomly. The volunteers were fed different meals containing 50g carbohydrates portion, the blood sample of diabetic volunteers were taken finger pricks at 0, 30, 60, 90, 120 and 180 minutes and normal volunteers 0, 15, 30, 45, 60, 90, 120 minutes and glycaemic index were calculated by standard formula. Results obtained in present study have suggested that all four test pizzas and chicken patty have very high glycaemic indices. It is therefore suggested that diabetic patients and high-risk families should not take all the test pizzas and chicken patty in their daily routine.

Classification of Diabetes Volunteers Based on Plasma Amino Acids Metabolic Profiling

To study the relation of plasma amino acids metabolic profiling and diabetes blood sugar level by using metabolomics, an on-line pre-column o-phthalic dicarboxaldehyde ( OPA) derivatization HPLC method for the relative quantitative determination of 21 amino acids in plasma samples was developed. The derivatization procedure was accomplished by an online auto-injector and the signals were detected with a UV detector. Mobile phase A was 10 mmol/L Na(2)HPO(4)-Na(2)B(4)O(7) buffer at pH 7.95, and B was acetonitrile-methanol-water (45:45:10 by volume). The elution program was 5% B at the start and 46% B at the end in 30 min. The 21 amino acids were satisfactorily separated in 27 min. Fifty-one plasma samples from diabetes volunteers were analyzed and were pre-divided into blood sugar ( B. S.) 9. 5 group. By SPSS and Matlab software platform, relation analysis was performed by using linear discriminant analysis, stepwise discriminant analysis, and scores plot models. By correlating the levels of blood sugar( B. S.) to 20 amino acids peak areas except glutamine, the results showed that the B. S. 9.5 group with a total hit ratio of 94.1%, stepwise discriminant analysis ( SDA) model indicated that 7 out of 20 amino acids,i.e., Arg, Cit, Leu, Asp, Asn, Thr and Trp essentially contributed to the above two groups division with the total hit ratio of 90.2%, which maybe have more means as potential marker groups for the early diagnosis of diabetes and in-depth research.

Use of slow release starch (SRS) to treat hypoglycaemia in type 1 diabetics

PurposeThe purpose of this paper is to evaluate if slow release starch (SRS) could be used to control/limit hypoglycaemia in type 1 diabetics.Design/methodology/approachTen type‐1 diabetic volunteers were fitted with continuous glucose monitors for two periods of 3 days when undertaking their normal routine or when consuming 60 g SRS before sleep.FindingsThe average number of nocturnal hypoglycaemic episodes where no SRS was consumed over 3 days was 2.7 ± 2.0 but only 0.7 ± 1.1 after SRS consumption before sleep. The duration of these events was equivalent to 318 ± 282 and 140 ± 337 min, respectively. Average nocturnal blood glucose concentration was 7.9 ± 1.4 mmol l−1 without SRS consumption but increased to 9.7 ± 2.7 mmol l−1 when SRS was consumed. These data were highly significant when subjected to analysis of variance (ANOVA) test on a subject by subject basis. The SRS may be used as a cost effective therapy to avoid hypoglycaemia in patients with type‐1 diabetes.Originality/valueThis paper reports for the first time the use of a physically modified waxy maize starch (SRS) to prevent/limit the incidence of nocturnal hypoglycaemia in type 1 diabetics.

Type 2 diabetes mellitus is associated with impaired cytokine response and adhesion molecule expression in human endotoxemia

Type 2 diabetes is associated with an increased risk of acquiring infectious diseases and developing sepsis. This may partly be due to immune dysfunction. We investigated the in vivo innate immune response of type 2 diabetic persons to an intravenous injection of E. coli lipopolysaccharide (LPS). After ethics approval, informed consent and a thorough physical examination, 19 type 2 diabetic patients and 23 healthy controls were included. LPS was given as an intravenous bolus injection of 0.3 ng/kg. Physiological variables, white blood cell count, and plasma concentrations of tumour necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and the adhesion molecules E-selectin, vascular adhesion molecule (VCAM)-1, and intracellular adhesion molecule (ICAM)-1 were measured hourly for 8 h. LPS injection induced a systemic inflammatory response with increases in neutrophils, temperature, heart rate and plasma concentrations of cytokines and adhesion molecules in healthy and type 2 diabetic volunteers. Type 2 diabetes was associated with less pronounced LPS-induced increases in TNF, IL-1ra, VCAM-1 and ICAM-1. There was a trend towards an attenuated upregulation of E-selectin in diabetics, even though the plasma concentration tended to be generally higher compared to healthy controls. Patients with type 2 diabetes exhibit an attenuated increase in plasma levels of TNF and IL-1ra, as well as an attenuated upregulation of VCAM-1 and ICAM-1 to LPS in vivo. This finding may provide a mechanistic explanation for the adverse outcome seen during infectious diseases in diabetic patients.

Evaluation of Hypoglycemic and Hypolipidemic Activity of Buteamonosperma Fruit in Diabetic Human Subjects

Evaluation of the hypoglycemic activity of local Butea monosperma (Palas papra) fruit in normal and diabetic human volunteers was conducted. Sampling was accomplished in and around the city of Faisalabad, especially at the Khadija Mahmood Trust Hospital and at the University of Agriculture, Faisalabad, Pakistan. Volunteers were categorized into normal and diabetic subjects on the basis of their blood glucose levels. Male and female diabetic volunteers aged between 30 and 60 years participated in the study. All the diabetic volunteers suffered from diabetes type II, i.e. non-insulin-dependent diabetes mellitus (NIDDM). The subjects were divided into 5 groups as follows: Group A - Untreated normal subjects; Group B - Normal subjects who received powdered B. monosperma (3 g) in 30 mL of water for 30 days, orally; Group C - Control diabetic subjects; Group D - Diabetic subjects who received powdered (3 g) in 30 mL of water for 30 days, orally; and Group E - Diabetic subjects who received a 5-mg tablet b. I. d. of Daonil® (a standard oral antidiabetic drug) in 30 mL of water for 30 days. The oral administration of B. monosperma fruit to diabetic and normal subjects for 30 days decreased (P < 0.05) blood glucose, urine sugar, and plasma glycoprotein levels, as well as the lipid profile and the activity of liver enzymes. In conclusion, the powder of the medicinal plant B. monosperma fruit can be considered an effective and alternative treatment for diabetes.

Human ATP synthase beta is phosphorylated at multiple sites and shows abnormal phosphorylation at specific sites in insulin-resistant muscle

Insulin resistance in skeletal muscle is linked to mitochondrial dysfunction in obesity and type 2 diabetes. Emerging evidence indicates that reversible phosphorylation regulates oxidative phosphorylation (OxPhos) proteins. The aim of this study was to identify and quantify site-specific phosphorylation of the catalytic beta subunit of ATP synthase (ATPsyn-beta) and determine protein abundance of ATPsyn-beta and other OxPhos components in skeletal muscle from healthy and insulin-resistant individuals. Skeletal muscle biopsies were obtained from lean, healthy, obese, non-diabetic and type 2 diabetic volunteers (each group n = 10) for immunoblotting of proteins, and hypothesis-driven identification and quantification of phosphorylation sites on ATPsyn-beta using targeted nanospray tandem mass spectrometry. Volunteers were metabolically characterised by euglycaemic-hyperinsulinaemic clamps. Seven phosphorylation sites were identified on ATPsyn-beta purified from human skeletal muscle. Obese individuals with and without type 2 diabetes were characterised by impaired insulin-stimulated glucose disposal rates, and showed a approximately 30% higher phosphorylation of ATPsyn-beta at Tyr361 and Thr213 (within the nucleotide-binding region of ATP synthase) as well as a coordinated downregulation of ATPsyn-beta protein and other OxPhos components. Insulin increased Tyr361 phosphorylation of ATPsyn-beta by approximately 50% in lean and healthy, but not insulin-resistant, individuals. These data demonstrate that ATPsyn-beta is phosphorylated at multiple sites in human skeletal muscle, and suggest that abnormal site-specific phosphorylation of ATPsyn-beta together with reduced content of OxPhos proteins contributes to mitochondrial dysfunction in insulin resistance. Further characterisation of phosphorylation of ATPsyn-beta may offer novel targets of treatment in human diseases with mitochondrial dysfunction, such as diabetes.

Proteomics Analysis of Human Skeletal Muscle Reveals Novel Abnormalities in Obesity and Type 2 Diabetes

OBJECTIVEInsulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Studies of insulin resistance usually are highly focused. However, approaches that give a more global picture of abnormalities in insulin resistance are useful in pointing out new directions for research. In previous studies, gene expression analyses show a coordinated pattern of reduction in nuclear-encoded mitochondrial gene expression in insulin resistance. However, changes in mRNA levels may not predict changes in protein abundance. An approach to identify global protein abundance changes involving the use of proteomics was used here.RESEARCH DESIGN AND METHODSMuscle biopsies were obtained basally from lean, obese, and type 2 diabetic volunteers (n = 8 each); glucose clamps were used to assess insulin sensitivity. Muscle protein was subjected to mass spectrometry–based quantification using normalized spectral abundance factors.RESULTSOf 1,218 proteins assigned, 400 were present in at least half of all subjects. Of these, 92 were altered by a factor of 2 in insulin resistance, and of those, 15 were significantly increased or decreased by ANOVA (P < 0.05). Analysis of protein sets revealed patterns of decreased abundance in mitochondrial proteins and altered abundance of proteins involved with cytoskeletal structure (desmin and alpha actinin-2 both decreased), chaperone function (TCP-1 subunits increased), and proteasome subunits (increased).CONCLUSIONSThe results confirm the reduction in mitochondrial proteins in insulin-resistant muscle and suggest that changes in muscle structure, protein degradation, and folding also characterize insulin resistance.

Acute effects of Fraxinus excelsior L. seed extract on postprandial glycemia and insulin secretion on healthy volunteers

Aim of the study Fraxinus excelsior L. (Family: Oleaceae) seeds are consumed as a food, condiment, and folk medicine. The seeds are traditionally used as a potent hypoglycemic agent, but no clinical evidence exists in as to this regard. We assessed the clinical efficacy and safety of the seed extract (FraxiPure™, Naturex), containing 6.8% of nuzhenide and 5.8% of GI3 (w/w), on plasma glucose and insulin levels against glucose (50 g) induced postprandial glycemia. Materials and methods Preselected dose (1.0 g) was used in a double blind, randomized, crossover, placebo (wheat bran) controlled study on 16 healthy volunteers. Each treatment was given immediately after a fasting blood glucose sample (0 min). Postprandial plasma glucose levels were estimated at 0, 15, 30, 45, 60, 90 and 120 min; and postprandial plasma insulin at 0, 30, 60, 90 and 120 min. Results The extract lowered the incremental postprandial plasma glucose concentration as compared to placebo at 45 min ( P = 0.06) and 120 min ( P = 0.07). It statistically ( P = 0.02) reduced the glycemic area under the blood glucose curve. The seed, also, induced a significant ( P = 0.002) secretion of insulin at 90 min after glucose administration. However, the insulinemic area under the blood insulin curve was not different than the placebo. No adverse events were reported. Conclusions Our findings confirm the hypoglycemic action of Fraxinus excelsior L. seed extract. These promising results, thus, encourage conducting long-term clinical studies to further evaluate the efficacy and safety of Fraxinus excelsior L. seed extract in healthy and diabetic volunteers and also to explore the possible mechanism(s) of action.

Microarray analysis of genes with impaired insulin regulation in the skeletal muscle of type 2 diabetic patients indicates the involvement of basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2)

One of the major processes by which insulin exerts its multiple biological actions is through gene expression regulation. Thus, the identification of transcription factors affected by insulin in target tissues represents an important challenge. The aim of the present study was to gain a greater insight into this issue through the identification of transcription factor genes with insulin-regulated expression in human skeletal muscle. Using microarray analysis, we defined the sets of genes modulated during a 3 h hyperinsulinaemic-euglycaemic clamp (2 mU min(-1) kg(-1)) in the skeletal muscle of insulin-sensitive control volunteers and in moderately obese insulin-resistant type 2 diabetic patients. Of the 1,529 and 1,499 genes regulated during the clamp in control and diabetic volunteers, respectively, we identified 30 transcription factors with impaired insulin-regulation in type 2 diabetic patients. Analysis of the promoters of the genes encoding these factors revealed a possible contribution of the transcriptional repressor basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2), insulin regulation of which is strongly altered in the muscle of diabetic patients. Gene ontology analysis of BHLHB2 target genes, identified after BHLHB2 overexpression in human primary myotubes, demonstrated that about 10% of the genes regulated in vivo during hyperinsulinaemia are potentially under the control of this repressor. The data also suggested that BHLHB2 is situated at the crossroads of a complex transcriptional network that is able to modulate major metabolic and biological pathways in skeletal muscle, including the regulation of a cluster of genes involved in muscle development and contraction. We have identified BHLHB2 as a potential novel mediator of insulin transcriptional action in human skeletal muscle.