Effects of Type II diabetes on capillary hemodynamics in skeletal muscle

2006 ◽  
Vol 291 (5) ◽  
pp. H2439-H2444 ◽  
Author(s):  
Danielle J. Padilla ◽  
Paul McDonough ◽  
Brad J. Behnke ◽  
Yutaka Kano ◽  
K. Sue Hageman ◽  
...  

Microcirculatory red blood cell (RBC) hemodynamics are impaired within skeletal muscle of Type I diabetic rats (Kindig CA, Sexton WL, Fedde MR, and Poole DC. Respir Physiol 111: 163–175, 1998). Whether muscle microcirculatory dysfunction occurs in Type II diabetes, the more prevalent form of the disease, is unknown. We hypothesized that Type II diabetes would reduce the proportion of capillaries supporting continuous RBC flow and RBC hemodynamics within the spinotrapezius muscle of the Goto-Kakizaki Type II diabetic rat (GK). With the use of intravital microscopy, muscle capillary diameter ( dc), capillary lineal density, capillary tube hematocrit (Hctcap), RBC flux ( FRBC), and velocity ( VRBC) were measured in healthy male Wistar (control: n = 5, blood glucose, 105 ± 5 mg/dl) and male GK ( n = 7, blood glucose, 263 ± 34 mg/dl) rats under resting conditions. Mean arterial pressure did not differ between groups ( P > 0.05). Sarcomere length was set to a physiological length (∼2.7 μm) to ensure that muscle stretching did not alter capillary hemodynamics; dc was not different between control and GK rats ( P > 0.05), but the percentage of RBC-perfused capillaries (control: 93 ± 3; GK: 66 ± 5 %), Hctcap, VRBC, FRBC, and O2 delivery per unit of muscle were all decreased in GK rats ( P < 0.05). This study indicates that Type II diabetes reduces both convective O2 delivery and diffusive O2 transport properties within muscle microcirculation. If these microcirculatory deficits are present during exercise, it may provide a basis for the reduced O2 exchange characteristic of Type II diabetic patients.

Author(s):  
Sagarika Majhi ◽  
Lubhan Singh

Introduction: Management of HIV/AIDS is gradually expanding to include the chronic and metabolic complications and the adverse effects associated with its treatments like Type II diabetes mellitus. Repaglinide is a novel oral hypoglycemic agent chemically unrelated to sulphonylureas, metformin or acarbose used for the treatment of type II diabetes. Nevirapine is widely used non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. Objective: The objective of this study was to examine the effect of oral administration of nevirapine on blood glucose and investigate their effect on the activity of repaglinide and to evaluate the safety and effectiveness of the combination. Materials and Methods: Studies in normal, diabetic rats and normal rabbits were conducted with oral doses of repaglinide, nevirapine and their combination. All the animals were fasted for 18 h prior to experimentation; during this period the animals were fed with water ad libitum. The blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours in rats by retro orbital puncture and by marginal ear vein puncture in rabbits at different time intervals. Further, the samples were analyzed for glucose by glucose oxidase/peroxidase (GOD/POD) method. The rabbit blood samples were analyzed by HPLC for serum repaglinide concentration. The serum repaglinide levels and pharmacokinetic parameters of repaglinide were evaluated with multiple dose treatments of nevirapine in rabbits. Result and Discussion: Nevirapine alone have no significant effect on the blood glucose level in rats and rabbits. Repaglinide produced hypoglycemic and antihyperglycemic activity in normal and diabetic rats with peak activity at 2 h and hypoglycemic activity in normal rabbits at 1.5 h. In combination, nevirapine reduced the effect of repaglinide in rats and rabbits. The interaction was found to be significant at both pharmacodynamic as well as at pharmacokinetic levels. Conclusion: Thus, it can be concluded that the combination of nevirapine and repaglinide may need dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. However, further studies are warranted.


2004 ◽  
Vol 82 (10) ◽  
pp. 888-894 ◽  
Author(s):  
Tod A Clark ◽  
Andrea L Edel ◽  
Clayton E Heyliger ◽  
Grant N Pierce

A novel black tea decoction containing vanadate has successfully replaced insulin in a rat model of insulin-dependent diabetes but is untested in non-insulin-dependent diabetic animals. A tea-vanadate decoction (TV) containing 30 or 40 mg sodium orthovanadate was administered by oral gavage to two groups of Zucker diabetic fatty rats and a conventional water vehicle containing 30 or 40 mg of sodium orthovanadate to two others. In the latter group receiving the 30-mg dose, vanadate induced diarrhea in 50% of the rats and death in 10%. In contrast, TV-treated rats had no incidence of diarrhea and no deaths. Symptoms were more severe in both groups with higher vanadate doses, so these were discontinued. After ~16 weeks, the level of vanadium in plasma and tissue extracts was negligible in a further group of untreated rats but highly elevated after vanadate treatment. Vanadium levels were not significantly different between the TV-treated diabetic rats and the diabetic rats given vanadate in a water vehicle. Over the 115 days of the study, blood glucose levels increased from ~17 to 25 mmol/L in untreated diabetic rats. This was effectively lowered (to <10 mmol/L) by TV treatment. Fasting blood glucose levels were 5, 7, and 20 mmol/L in control (nondiabetic, untreated), TV-treated and untreated diabetic rats, respectively. Rats required treatment with TV for only ~50% of the days in the study. Increase in body mass during the study was significantly lower in untreated diabetic rats (despite higher food intake) than the other groups. Body mass gain and food intake were normal in TV-treated rats. Water intake was 28 mL/rat daily in control rats, 130 mL/rat daily in untreated diabetic rats, and 52 mL/rat daily in TV-treated diabetic rats. Plasma creatinine and aspartate aminotransferase levels were significantly depressed in untreated diabetic rats, and TV treatment normalized this. Our results demonstrate that a novel oral therapy containing black tea and vanadate possesses a striking capacity to regulate glucose and attenuates complications in a rat model of type II diabetes. Key words: diabetes mellitus, tea, glycemia, type II diabetes.


2005 ◽  
Vol 33 (2) ◽  
pp. 354-357 ◽  
Author(s):  
M. Björnholm ◽  
J.R. Zierath

Type II diabetes is characterized by defects in insulin action on peripheral tissues, such as skeletal muscle, adipose tissue and liver and pancreatic β-cell defects. Since the skeletal muscle accounts for approx. 75% of whole body insulin-stimulated glucose uptake, defects in this tissue play a major role in the impaired glucose homoeostasis in Type II diabetic patients. Thus identifying defective steps in this process may reveal attractive targets for drug development to combat insulin resistance and Type II diabetes. This review will describe the effects of insulin on glucose transport and other metabolic events in skeletal muscle that are mediated by intracellular signalling cascades. Evidence for impaired activation of the insulin receptor signalling cascade and defective glucose transporter 4 translocation in the skeletal muscle from Type II diabetic patients will be presented. Through the identification of the intracellular defects in insulin action that control glucose homoeostasis, a better understanding of the disease pathogenesis can be gained and strategies for intervention may be developed.


2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
J. Fuentes-Antrás ◽  
B. Picatoste ◽  
A. Gómez-Hernández ◽  
J. Egido ◽  
J. Tuñón ◽  
...  

Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by changes in energy substrates and occurs in the absence of atherothrombosis, hypertension, or other cardiomyopathies. Inflammation, hypertrophy, fibrosis, steatosis, and apoptosis in the myocardium have been studied in numerous diabetic experimental models in animals, mostly rodents. Type I and type II diabetes were induced by genetic manipulation, pancreatic toxins, and fat and sweet diets, and animals recapitulate the main features of human diabetes and related cardiomyopathy. In this review we update and discuss the main experimental models of diabetic cardiomyopathy, analysing the associated metabolic, structural, and functional abnormalities, and including current tools for detection of these responses. Also, novel experimental models based on genetic modifications of specific related genes have been discussed. The study of specific pathways or factors responsible for cardiac failures may be useful to design new pharmacological strategies for diabetic patients.


2020 ◽  
Vol 36 (3) ◽  
Author(s):  
Alia Ali Muhammed ◽  
Azeem Taj ◽  
Muhammed Uthman Ahmed ◽  
Elsa Tabrez

Objectives: To determine the frequency of impaired fasting glucose in first degree relatives of people with Type-II diabetes and its association with BMI. Methods: This cross-sectional study was conducted in Diabetic clinic of Shaikh Zayed Hospital, Lahore from July to December 2017. Individuals aged ≥35 years, first degree relatives of people with Type-II diabetes, were selected and their fasting blood glucose levels were checked twice a week apart. Study participants were divided into 3 groups. Group-I were those with normal fasting blood glucose (FBS: <100mg/dl), Group-II were those with impaired fasting glucose (100-125mg/dl), considered as high risk and Group-III included those who turned out to be having frank diabetes (FBS: ≥126mg/dl). Exclusion criteria were known diabetes and pregnancy. Proportions of impaired fasting glucose levels versus BMI were compared using Chi-square test. Significance was considered at P <0.001. Results: A total of hundred subjects were included in the study with the mean age of 44.27 years. Sixty percent participants had normal FBS, 31% showed impaired FBS and 09% had frank diabetes (P <0.001). Significant association was found between impaired fasting glucose and BMI, as with increasing BMI the frequency of impaired fasting glucose increases. Conclusion: First-degree relatives of people with Type-II diabetes showed higher frequency of impaired fasting glucose and obesity was an important risk factor. doi: https://doi.org/10.12669/pjms.36.3.57 How to cite this:Ali A, Taj A, Ahmed MU, Tabrez E. Frequency of impaired fasting glucose in first degree relatives of Type-II diabetic patients and its association with Body Mass Index. Pak J Med Sci. 2020;36(3):407-411. doi: https://doi.org/10.12669/pjms.36.3.57 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Top Drugs ◽  
2015 ◽  
Author(s):  
Jie Jack Li

Diabetes has been known since antiquity. In fact, the term “diabetes mellitus” comes from the Greek meaning “siphon and honey” due to the excess excretion (siphon or faucet) of hyperglycemic (sweetened, or honeyed) urine associated with diabetes. In ancient times, diabetes was mostly type I, which usually manifests acutely in the young, secondary to certain underlying insults (possibly infections) to the islet cells of the pancreas resulting in an absolute lack of insulin. Insulin was discovered by Banting and Best in 1921, and insulin injection has literally saved millions of lives since then. With the wondrous efficacy that insulin bestows, type I diabetes is largely controlled because type I diabetes is insulindependent. However, type II diabetes, a more prevalent form of diabetes, is not insulin-dependent. In ancient times, when nutrition was scarce and obesity was not prevalent, type II diabetes mellitus (T2DM) was extremely rare. Indeed, type II diabetes is a disease more frequently associated with maturity, obesity, and gradually increasing blood glucose concentrations, and it may be asymptomatic for some time, only discovered on routine glucose screening. In fact, with the increasing body weight of the general population of the developed world, type II diabetes is becoming an epidemic. Serious complications of diabetes include nephropathy (kidney diseases), neuropathy (nerve damage), and retinopathy (blindness). Diabetes is the most common cause of blindness and amputation in the elderly in the United States. Oral diabetes drugs are required for most type II diabetic patients. Diabetes drugs may be classified into four categories: (a) agents that augment the supply of insulin such as sulfonylureas; (b) agents that enhance the effectiveness of insulin such as biguanides and thiazolidinediones; (c) GLP agonists; and (d) DPP4 Inhibitors. The efficacy of all the antidiabetic drugs can be monitored by measuring glycosylated hemoglobin (HaA1c) as a long term marker of elevated blood glucose. The amount of HaA1c reflects the average level over the last 120 days, the life span of a red blood cell, and should remain below 7%.


2021 ◽  
pp. 78-80
Author(s):  
Barnali Bhattacharyya Thakur ◽  
Keshab Bora ◽  
Sherin Gogoi

INTRODUCTION: Diabetes mellitus is a major public health problem with signicant morbidity and mortality. Diabetic retinopathy is one of the most common microvascular complications of Diabetes mellitus causing blindness. Vitamin D is a fat soluble vitamin involved in maintenance of mineral homeostasis and bone remodelling. Vitamin D deciency is highly prevalent in type I and type II Diabetes. 38 diabetic without ocular disease a METHOD: nd 30 diabetic with retinopathy were taken as cases and 38 age sex matched healthy persons were taken as controls. Serum Vit D and glucose were estimated and retinopathy was diagnosed by fundus examination. The results were statistically analysed. Statistica RESULTS: l analysis of the results shows a negative correlation between FBS and HbA1C with Vitamin D level in diabetic retinopathy patients. Patients CONCLUSION: with Diabetic retinopathy has lower serum Vitamin D level than diabetic patients without retinopathy.


2010 ◽  
Vol 109 (5) ◽  
pp. 1347-1353 ◽  
Author(s):  
Steven W. Copp ◽  
K. Sue Hageman ◽  
Brad J. Behnke ◽  
David C. Poole ◽  
Timothy I. Musch

The purpose of the present investigation was to examine the muscle hyperemic response to steady-state submaximal running exercise in the Goto-Kakizaki (GK) Type II diabetic rat. Specifically, the hypothesis was tested that Type II diabetes would redistribute exercising blood flow toward less oxidative muscles and muscle portions of the hindlimb. GK diabetic ( n = 10) and Wistar control ( n = 8, blood glucose concentration, 13.7 ± 1.6 and 5.7 ± 0.2 mM, respectively, P < 0.05) rats were run at 20 m/min on a 10% grade. Blood flows to 28 hindlimb muscles and muscle portions as well as the abdominal organs and kidneys were measured in the steady state of exercise using radiolabeled 15-μm microspheres. Blood flow to the total hindlimb musculature did not differ between GK diabetic and control rats (161 ± 16 and 129 ± 15 ml·min−1·100g−1, respectively, P = 0.18). Moreover, there was no difference in blood flow between GK diabetic and control rats in 20 of the individual muscles or muscle parts examined. However, in the other eight muscles examined that typically are comprised of a majority of fast-twitch glycolytic (IIb/IIdx) fibers, blood flow was significantly greater (i.e., ↑31–119%, P < 0.05) in the GK diabetic rats. Despite previously documented impairments of several vasodilatory pathways in Type II diabetes these data provide the first demonstration that a reduction of exercising muscle blood flow during submaximal exercise is not an obligatory consequence of this condition in the GK diabetic rat.


2009 ◽  
Vol 136 (5) ◽  
pp. A-584-A-585 ◽  
Author(s):  
Jie Chen ◽  
Jieyun Yin ◽  
Lin Lin ◽  
Pankaj J. Pasricha ◽  
Jiande Chen

2019 ◽  
Vol 7 (1) ◽  
pp. 1-4
Author(s):  
Alekhya Ayalapuram

With changing lifestyle and increasing obesity, prevalence of type -II Diabetes Mellitus is increasing in geriatric individuals, who are generally prone to tooth loss. As a result the demand for implants in these patients is also increasing and planning implants has been a challenge to present day dentists. Diabetes Mellitus causes impaired metabolism in general, especially bone metabolism resulting in impaired Osseointegration and poor wound healing. Growing demand of implants in Type II DM patients has initiated research towards implants survival rates. Extensive research till now states - poorly controlled diabetic patients have higher implant failure rates, where as Diabetic patients with controlled blood glucose levels respond to implants in similar way as healthy patients. The present article is one such trail to confirm that type II Diabetes Mellitus is no more contra-indication for Implants till Blood glucose levels are controlled to normal levels. Key words: Type-II Diabetes Mellitus; Two-piece implant; Delayed loading;


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