scholarly journals Impaired Insulin-Stimulated Expression of the Glycogen Synthase Gene in Skeletal Muscle of Type 2 Diabetic Patients Is Acquired Rather Than Inherited1

2000 ◽  
Vol 85 (4) ◽  
pp. 1584-1590 ◽  
Author(s):  
Xudong Huang ◽  
Allan Vaag ◽  
Mona Hansson ◽  
Jianping Weng ◽  
Esa Laurila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Mrna Expression ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Control Subjects ◽  
Chronic Hyperglycemia

To examine whether defective muscle glycogen synthase (GYS1) expression is associated with impaired glycogen synthesis in type 2 diabetes and whether the defect is inherited or acquired, we measured GYS1 gene expression and enzyme activity in muscle biopsies taken before and after an insulin clamp in 12 monozygotic twin pairs discordant for type 2 diabetes and in 12 matched control subjects. The effect of insulin on GYS1 fractional activity, when expressed as the increment over the basal values, was significantly impaired in diabetic (15.7 ± 3.3%; P < 0.01), but not in nondiabetic (23.7 ± 1.8%; P = NS) twins compared with that in control subjects (28.1 ± 2.3%). Insulin increased GYS1 messenger ribonucleic acid (mRNA) expression in control subjects (from 0.14 ± 0.02 to 1.74 ± 0.10 relative units; P < 0.01) and in nondiabetic (from 0.24 ± 0.05 to 1.81 ± 0.16 relative units; P < 0.01) and diabetic (from 0.20 ± 0.07 to 1.08 ± 0.14 relative units; P < 0.01) twins. The effect of insulin on GYS1 expression was, however, significantly reduced in the diabetic (P < 0.003), but not in the nondiabetic, twins compared with that in control subjects. The postclamp GYS1 mRNA levels correlated strongly with the hemoglobin A1c levels (r = −0.61; P < 0.001). Despite the decrease in postclamp GYS1 mRNA levels, the GYS1 protein levels were not decreased in the diabetic twins compared with those in the control subjects (2.10 ± 0.46 vs. 2.10 ± 0.34 relative units; P = NS). We conclude that 1) insulin stimulates GYS1 mRNA expression; and 2) impaired stimulation of GYS1 gene expression by insulin in patients with type 2 diabetes is acquired and most likely is secondary to chronic hyperglycemia.

scholarly journals A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum

2019 ◽  
Vol 20 (13) ◽  
pp. 3257 ◽  
Author(s):  
Sophie Gravel ◽  
Benoit Panzini ◽  
Francois Belanger ◽  
Jacques Turgeon ◽  
Veronique Michaud
Keyword(s):  
Type 2 Diabetes ◽  
Mrna Expression ◽  
Drug Metabolizing Enzymes ◽  
Mrna Levels ◽  
Metabolizing Enzymes ◽  
Expression Levels ◽  
The Impact ◽  
Duodenal Biopsies ◽  
Mrna Expression Levels

To characterize effects of type 2 diabetes (T2D) on mRNA expression levels for 10 Cytochromes P450 (CYP450s), two carboxylesterases, and three drug transporters (ABCB1, ABCG2, SLCO2B1) in human duodenal biopsies. To compare drug metabolizing enzyme activities of four CYP450 isoenzymes in duodenal biopsies from patients with or without T2D. mRNA levels were quantified (RT-qPCR) in human duodenal biopsies obtained from patients with (n = 20) or without (n = 16) T2D undergoing a scheduled gastro-intestinal endoscopy. CYP450 activities were determined following incubation of biopsy homogenates with probe substrates for CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2J2 (ebastine), and CYP3A4/5 (midazolam). Covariables related to inflammation, T2D, demographic, and genetics were investigated. T2D had no major effects on mRNA levels of all enzymes and transporters assessed. Formation rates of metabolites (pmoles mg protein−1 min−1) determined by LC-MS/MS for CYP2C9 (0.48 ± 0.26 vs. 0.41 ± 0.12), CYP2J2 (2.16 ± 1.70 vs. 1.69 ± 0.93), and CYP3A (5.25 ± 3.72 vs. 5.02 ± 4.76) were not different between biopsies obtained from individuals with or without T2D (p > 0.05). No CYP2B6 specific activity was measured. TNF-α levels were higher in T2D patients but did not correlate with any changes in mRNA expression levels for drug metabolizing enzymes or transporters in the duodenum. T2D did not modulate expression or activity of tested drug metabolizing enzymes and transporters in the human duodenum. Previously reported changes in drug oral clearances in patients with T2D could be due to a tissue-specific disease modulation occurring in the liver and/or in other parts of the intestines.

scholarly journals Intermuscular Fat Content in Young Chinese Men With Newly Diagnosed Type 2 Diabetes: Based on MR mDIXON-Quant Quantitative Technique

2021 ◽  
Vol 12 ◽  
Author(s):  
Fuyao Yu ◽  
Bing He ◽  
Li Chen ◽  
Fengzhe Wang ◽  
Haidong Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fat Content ◽  
Control Group ◽  
Diabetic Patients ◽  
Diabetes Group ◽  
Control Subjects ◽  
Intermuscular Fat ◽  
And Control

ObjectiveSkeletal muscle fat content is one of the important contributors to insulin resistance (IR), but its diagnostic value remains unknown, especially in the Chinese population. Therefore, we aimed to analyze differences in skeletal muscle fat content and various functional MRI parameters between diabetic patients and control subjects to evaluate the early indicators of diabetes. In addition, we aimed to investigate the associations among skeletal muscle fat content, magnetic resonance parameters of skeletal muscle function and IR in type 2 diabetic patients and control subjects.MethodsWe enrolled 12 patients (age:29-38 years, BMI: 25-28 kg/m2) who were newly diagnosed with type 2 diabetes (intravenous plasma glucose concentration≥11.1mmol/l or fasting blood glucose concentration≥7.0mmol/l) together with 12 control subjects as the control group (age: 26-33 years, BMI: 21-28 kg/m2). Fasting blood samples were collected for the measurement of glucose, insulin, 2-hour postprandial blood glucose (PBG2h), and glycated hemoglobin (HbAlc). The magnetic resonance scan of the lower extremity and abdomen was performed, which can evaluate visceral fat content as well as skeletal muscle metabolism and function through transverse relaxation times (T2), fraction anisotropy (FA) and apparent diffusion coefficient (ADC) values.ResultsWe found a significant difference in intermuscular fat (IMAT) between the diabetes group and the control group (p<0.05), the ratio of IMAT in thigh muscles of diabetes group was higher than that of control group. In the entire cohort, IMAT was positively correlated with HOMA-IR, HbAlc, T2, and FA, and the T2 value was correlated with HOMA-IR, PBG2h and HbAlc (p<0.05). There were also significant differences in T2 and FA values between the diabetes group and the control group (p<0.05). According to the ROC, assuming 8.85% of IMAT as the cutoff value, the sensitivity and specificity of IMAT were 100% and 83.3%, respectively. Assuming 39.25ms as the cutoff value, the sensitivity and specificity of T2 value were 66.7% and 91.7%, respectively. All the statistical analyses were adjusted for age, BMI and visceral fat content.ConclusionDeposition of IMAT in skeletal muscles seems to be an important determinant for IR in type 2 diabetes. The skeletal muscle IMAT value greater than 8.85% and the T2 value greater than 39.25ms are suggestive of IR.

scholarly journals Glycaemic Regulation with Zinc Combination in Type 2 Diabetes Mellitus

2021 ◽  
pp. 33-37
Author(s):  
Gangaram Bhadarge ◽  
Pratibha Dawande ◽  
Nandkishor Bankar ◽  
Raunak Kotecha
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Zn Deficiency ◽  
Diabetic Patients ◽  
Chronic Hyperglycemia ◽  
Low Levels

Introduction: Zn supplementation improved glutathione peroxidase enzyme activity and decreased malondialdehyde and nitric oxide levels in diabetic rats, revealing Zn's defensive effect against oxidative stress in type 2 diabetes. The investigators have discovered that consuming Zn increased liver function and protected pancreatic tissue from damage caused by diabetes. Since Zn also prevents chronic hyperglycemia, it helps to minimize oxidative stress caused by type 2 diabetes. Diabetes mellitus (DM) is a global health problem that affects more than 3 million people worldwide (16% of population). Chronic hyperglycemia causes oxidative stress in diabetic patients by the development of free radicals (oxidants) and lowering the antioxidant protection mechanism. Aim: Glycaemic Regulation with Zinc Combination in Type 2 Diabetes Mellitus. Materials and Methods: Faculty of Medicine and Diabetic Opd, Datta Meghe Mediсаl Соllege and Shаlinitаi Meghe Hоsрitаl аnd Reseаrсh Сenter, Nаgрur in соllаbоrаtion with Dаttа Meghe Institute оf Mediсаl Sсienсes Deemed to be University, Sаwаngi, Wаrdhа, Mаhаrаshtrа. Results: The mean Zn level was 12.213±2.342in all participants and 9.121±1.782 in the control group, whereas it was significantly low (9.121±1.782) in the diabetic group, and there was statistically significant difference in Zn levels between the controls and the diabetic group (P < 0.001).FBS, HbA1C, serum Zinc mean effects between control and patients showed statistically significant differences in type 2 diabetes mellitus (P <0.0001). Conclusion: Our findings show that people with diabetes have lower levels of Zn than healthy people. The cause and effect of the association between very low levels of Zn and the progression of diabetes, or diabetes that causes Zn deficiency, is still unknown. Low levels of Zn are associated with poor glycemic control, and poor glycemic control is a good indication of Zn deficiency, as there was a negative association between serum Zn and FBS and HBA1C. If diabetic patients have low glycemic regulation, a long history of diabetes, obesity, or are over the age of 50, we look to assess their levels in Zn so that Zn alternative treatment can begin to release oxidative stress in this high-risk group.

scholarly journals Isometric knee extension force in Japanese type 2 diabetic patients without apparent diabetic polyneuropathy: Data from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study

2019 ◽  
Vol 7 ◽  
pp. 205031211882341 ◽  
Author(s):  
Takuo Nomura ◽  
Tomoyasu Ishiguro ◽  
Masayoshi Ohira ◽  
Hiroyuki Oka ◽  
Yukio Ikeda
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Polyneuropathy ◽  
Knee Extension ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Multicenter Survey ◽  
Isometric Knee Extension ◽  
Extension Force ◽  
Healthy Control

Objectives: To determine standard reference values for isometric knee extension force using a cohort of Japanese type 2 diabetic patients without diabetic polyneuropathy. Methods: Patient data were collected from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study and compared with previously published data of healthy control subjects. In total, we enrolled 898 patients with type 2 diabetes aged 30–87 years, who did not have diabetic polyneuropathy. The control group included 510 healthy subjects aged 30–88 years. Maximum isometric knee extension force (KEF) values were obtained by using a hand-held dynamometer with belt stabilization. In addition, KEF (kgf) was adjusted for bodyweight (kg) to calculate %KEF. Results: KEF and %KEF decreased with age in both patients with diabetes and healthy control subjects. The mean values of KEF and %KEF in patients with diabetes were reduced by 9.7% and 20.8%, respectively, in males, and by 11.6% and 23.0%, respectively, in females compared to the values in healthy control subjects. Conclusion: KEF and %KEF in patients with type 2 diabetes without diabetic polyneuropathy may reduce by approximately 10% and 20%, respectively, compared to these values in healthy control subjects. This study provides reference values for isometric KEF with respect to sex in a population covering a wide age range.

scholarly journals Thyroid profile in type 2 diabetes mellitus

2019 ◽  
Vol 6 (6) ◽  
pp. 1906
Author(s):  
Mahesh Dave ◽  
Hazari Lal Saini ◽  
Ankit Gupta ◽  
Jitendra Singh Choudhary ◽  
Aniruddha Burli
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Thyroid Dysfunction ◽  
Diabetic Patients ◽  
Thyroid Disorder ◽  
Chronic Hyperglycemia ◽  
Organ Systems ◽  
Thyroid Profile

Background: Diabetes mellitus is an endocrine disorder which involves multiple organ systems and leads to significant morbidity and mortality. Diabetes mellitus has been defined as “A metabolic syndrome characterized by chronic hyperglycemia and disturbance of carbohydrate, fat and protein metabolism associated with absolute or relative deficiency in insulin secretion and or insulin action”. Thyroid diseases are also a common endocrinopathy seen in the adult population. Thyroid hormones are intimately involved in cellular metabolism. The present work is a modest attempt to study the prevalence of thyroid disorders in patients with type 2 diabetes mellitus.Methods: The study was carried out in total 108 diabetic patients without known thyroid disorder admitted in various Medical wards of R.N.T. Medical college and attached group of hospitals, Udaipur. It was a cross Sectional study done over a period of 10 months. Results: In the present study, 13% of patients with type 2 diabetes mellitus had abnormal thyroid profile. Out of which the most common presentation was sub clinical hypothyroidism found in 9.25% followed by1.9% had overt hypothyroidism and 1.9% had sub clinical hyperthyroidism. In persons with abnormal thyroid profile 85.7% were females and 14.3% were males which was statistically significant.Conclusions: Prevalence of thyroid dysfunction is common among T2DM patients and is higher in females than in males. There is no significant correlation between thyroid dysfunction and age, diabetes control, family history, type of treatment and HbA1c level in diabetic patients.

scholarly journals Identification of Perturbed Pathways Rendering Susceptibility to Tuberculosis in Type 2 Diabetes Mellitus Patients Using BioNSi Simulation of Integrated Network of Implicated Human Genes

2021 ◽  
Author(s):  
Jyoti Rani ◽  
Anasuya Bhargav ◽  
Malabika Datta ◽  
Urmi Bajpai ◽  
Srinivasan Ramachandran
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
P Value ◽  
Receptor Signaling ◽  
Chronic Hyperglycemia

Abstract Adaptive immune response of the Th1 arm is the main defense against tuberculosis (TB). However, in Type 2 Diabetes Mellitus (T2DM) patients, chronic hyperglycemia and inflammation underlie susceptibility to TB and results in poor TB control. The molecular pathways causing susceptibility of diabetics to tuberculosis is not fully understood. Here, an integrative pathway-based approach is used to investigate the perturbed pathways in T2DM patients rendering susceptibility to TB. We obtained 36 genes implicated in the Type 2 diabetes associated tuberculosis (T2DMTB) from literature. Gene expression analysis on T2DM patients’ data (GSE28168) showed that DEFA1 is differentially expressed at Padj < 0.05. The genes CAMP, CD14, CORO1A, LAMP1, TLR4, IL17F and SOCS3 were differentially expressed in T2DM patients at P value < 0.05. 7 microRNAs associated with these T2DMTB genes were obtained from NetworkAnalyst and verified for their literature evidences. The hsa-miR-146a microRNA was differentially expressed at Padj < 0.05. The human host TB susceptibility genes TNFRSF10A, MSRA, GPR148, SLC37A3, PXK, PROK2, REV3L, PGM1, HIST3H2A, PLAC4, LETM2, EMP2 and were also differentially expressed at Padj < 0.05. We included all these genes and added the remaining 28 genes from the T2DMTB set and the rest of differentially expressed genes at Padj < 0.05 in STRING and obtained a well-connected network with high confidence score greater than 0.7. From this network we extracted the KEGG pathways at FDR < 0.05 and retained only Diabetes and TB pathways among the disease pathways. The network was simulated with BioNSi using gene expression data from GSE26168. The Necroptosis pathway showed the maximum perturbations in T2DM patients, followed by NOD-like receptor signaling, Toll-like receptor signaling, NF-kappa-B signaling and MAPK signaling. These pathways likely underlie susceptibility to TB in T2DM patients.

scholarly journals Detection of Cytomorphological Changes in Buccal Mucosal Cells of Type 2 Diabetic Patients Using Oral Exfoliative Cytology

2017 ◽  
Vol 23 (2) ◽  
Author(s):  
Sadia Sharif ◽  
Naureen Sarwar ◽  
Bushra Nisar ◽  
Muhammad Khalid Masood ◽  
Asim Hameed
Keyword(s):  
The Body ◽  
P Value ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Control Subjects ◽  
Nuclear Diameter ◽  
Chronic Hyperglycemia ◽  
Mucosal Cells ◽  
Type 2 Diabetic

AbstractBackground:  Diabetes mellitus is an extremely common endocrine metabolic disorder that results in chronic hyperglycemia. It has effects on various tissues of the body. Due to this increased blood glucose levels considerable cellular changes occur in oral cavity as well. This field has attracted little research. The aim of the study was to analyze the changes in morphology and cytomorphometric measurements in the buccal mucosal cells of type 2 diabetic patients.Objectives:  The Objective of this study was to detect the cytological and morphological alterations of oral epithelial cells, in type 2 diabetic patients and healthy control subjects in exfoliated cytology smears, to com-pare the cytoplasmic diameter, nuclear diameter, and nucleus: cytoplasm ratio in type 2 diabetics and heal-thy control subjects and to analyze the above mentioned cellular alterations in patients with controlled and uncontrolled diabetes.Methods:  Cross-sectional analysis was performed in three groups on the bases of HbA1c levels. Group 1 was uncontrolled diabetics with HbA1C ≥ 7.0%, Gro-up 2 was well controlled diabetics with HbA1c ≤ 7.0% and Group 3 was Control healthy having HbA1C ≤ 5. 6%. Smears from normal buccal mucosa were obtai-ned from each subject and stained with Papanicolaou method. An eyepiece micrometer was used to take mean values of ND, CyD, and N: C ratio. Fifty (50) clearly defined cells were measured in each case in a step wise manner, to evade quantifying cells once more. Comparison of Nuclear Diameter (ND), Cytoplasmic Diameter (CY D) and ratio of two Diameters (N: C) among three groups was performed by using ANOVA. TUKEY’S test for post –hoc analysis was used where required.Results:  The variability in diameter of nucleus among all three sample groups showed significant p-value < 0.001.Whereas the measurement for cytoplasmic diameter between three groups was not significant (p-value 0.178). The ratio of nuclear diameter to cytoplasmic diameter calculated was significant (p-value < 0.001). Hence it proved from the results that considerably exaggerated ND and N: C ratios were seen as the glycemic control (HbA1C) is poorer.Conclusion:  The results suggested that nuclear size of buccal mucosal cells increased in type 2 diabetic pati-ents while no change was observed in cytoplasmic dimensions.

Abstract 458: Omega-3 Supplementation Does Not Affect Inflammatory Gene Expression in the Small Intestine of Patients with Type 2 Diabetes

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Marie-ève Labonté ◽  
Patrick Couture ◽  
André J Tremblay ◽  
Jean-Charles Hogue ◽  
Valéry Lemelin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Small Intestine ◽  
Mrna Expression ◽  
Omega 3 ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Anti Inflammatory ◽  
The Impact

Recent evidence suggests that diet-induced inflammation in the small intestine is linked to obesity and insulin resistance. Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to have anti-inflammatory effects by down-regulating inflammatory gene expression in adipocytes and mononuclear cells. However, the extent to which EPA and DHA may exert their anti-inflammatory effects by down-regulating inflammation in the gut is unknown. The objective of the study was to investigate the impact of EPA+DHA supplementation on the expression of inflammatory genes in the small intestine of patients with type 2 diabetes. A total of 12 men with type 2 diabetes were recruited in this placebo-controlled randomized crossover study. After a 4-week run-in period, patients received in random sequence 5 g/d of fish oil providing 3 g of EPA+DHA or placebo (corn and soybean oil) for 8 weeks, each separated by a 12-week washout period. Gene expression was assessed by real-time PCR in duodenal biopsy samples obtained in the fasted state at the end of each treatment phase. Intestinal mRNA expression levels for interleukin(IL)-6 and tumor-necrosis factor(TNF)-α were hardly detectable after either treatment (< 100 copies/10^5 copies of the reference gene ATP synthase O subunit, ATP5o). Intestinal mRNA expression of IL-18 and of the transcription factor STAT3 (signal transducer and activator of transcription 3) was higher (> 5000 copies/10^5 copies ATP5o) but still relatively low and EPA+DHA supplementation had no impact on any of these levels (P ≥ 0.73 between treatments). Plasma C-reactive protein (CRP) concentrations after supplementation with EPA+DHA (5.2 ± 4.5 mg/L) were not significantly different than values measured after placebo (8.0 ± 10.8 mg/L, P = 0.2). In conclusion, these data suggest that gene expression of pro-inflammatory cytokines and STAT3 in duodenal cells is low in patients with type 2 diabetes and not affected by EPA+DHA supplementation.

Abstract 024: MicroRNAs and Anesthetic Cardioprotection in Diabetes

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Zeljko J Bosnjak ◽  
Jessica Olson ◽  
Alison Kriegel ◽  
Xiaowen Bai ◽  
Mingyu Liang
Keyword(s):  
Type 2 Diabetes ◽  
Stem Cells ◽  
Mitochondrial Permeability Transition ◽  
Glycogen Synthase ◽  
Patient Specific ◽  
Diabetic Patients ◽  
Human Cardiomyocytes ◽  
Cardiovascular Morbidity And Mortality ◽  
Wide Range

Introduction: MicroRNAs are endogenous small RNA molecules that regulate a wide range of cellular functions primarily through reduction of target protein expression. Several microRNAs have been shown to play important roles in cardiac injury, and also contribute to the development of diabetic complications and cardiac preconditioning. We utilized a model of the patient-specific induced pluripotent stem cells (iPSCs) differentiated into the cardiac lineage in order to delineate the environmental and cellular mechanisms responsible for overturning anesthetic cardioprotection in diabetes. We hypothesized that miR-21 contributes to cardioprotection conferred by anesthetics in human cardiomyocytes and that diabetic conditions compromise this protection in part via suppression of miR-21. Methods: We have developed and validated a clinically relevant model of cardioprotection using human cardiomyocytes differentiated from the iPSCs derived from non-diabetic individuals (N-CM) and patients with type 2 diabetes mellitus (T2-CM). Results: Our results indicate that cardiomyocytes derived from type 2 diabetes-specific stem cells recapitulate the phenotypic findings from type 2 diabetic patients. For instance, T2-CM exhibited a suppression of protein kinase B (Akt) and activation of glycogen synthase kinase-3β, compared to N-CM; indicating that this pathway is compromised in cardiomyocytes derived from diabetic individuals. In addition, we examined whether isoflurane could delay oxidative stress-induced mitochondrial permeability transition pore (mPTP) opening in T2-CM and found that the effects of isoflurane were significantly attenuated as compared to N-CM. Finally, isoflurane increased miR-21 abundance in N-CM, but not in T2-CM. Summary: Diabetes and hyperglycemia substantially increase perioperative cardiovascular risk, with few mitigating strategies. Our data indicate an important role of miR-21 in isoflurane-induced cardioprotection and its impairment by diabetic conditions that may suggest new therapeutic targets for reducing perioperative cardiovascular morbidity and mortality in high-risk patients.

Altered energetic properties in skeletal muscle of men with well-controlled insulin-dependent (type 1) diabetes

2003 ◽  
Vol 284 (4) ◽  
pp. E655-E662 ◽  
Author(s):  
Gregory J. Crowther ◽  
Jerrold M. Milstein ◽  
Sharon A. Jubrias ◽  
Martin J. Kushmerick ◽  
Rodney K. Gronka ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Glycolytic Flux ◽  
Resonance Spectroscopy ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Energetic Properties ◽  
Insulin Dependent

This study asked whether the energetic properties of muscles are changed by insulin-dependent diabetes mellitus (or type 1 diabetes), as occurs in obesity and type 2 diabetes. We used 31P magnetic resonance spectroscopy to measure glycolytic flux, oxidative flux, and contractile cost in the ankle dorsiflexor muscles of 10 men with well-managed type 1 diabetes and 10 age- and activity-matched control subjects. Each subject performed sustained isometric muscle contractions lasting 30 and 120 s while attempting to maintain 70–75% of maximal voluntary contraction force. An altered glycolytic flux in type 1 diabetic subjects relative to control subjects was apparent from significant differences in pH in muscle at rest and at the end of the 120-s bout. Glycolytic flux during exercise began earlier and reached a higher peak rate in diabetic patients than in control subjects. A reduced oxidative capacity in the diabetic patients' muscles was evident from a significantly slower phosphocreatine recovery from a 30-s exercise bout. Our findings represent the first characterization of the energetic properties of muscle from type 1 diabetic patients. The observed changes in glycolytic and oxidative fluxes suggest a diabetes-induced shift in the metabolic profile of muscle, consistent with studies of obesity and type 2 diabetes that point to common muscle adaptations in these diseases.

Sign in / Sign up

Export Citation Format

Share Document