Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart

1996 ◽  
Vol 271 (1) ◽  
pp. H192-H202 ◽  
Author(s):  
C. E. Flarsheim ◽  
I. L. Grupp ◽  
M. A. Matlib
Keyword(s):  
Atp Synthesis ◽  
Insulin Dependent Diabetes Mellitus ◽  
Work Load ◽  
Diabetic Rats ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Rat ◽  
Synthesis Rate ◽  
Insulin Dependent ◽  
And Control ◽  
Stimulation Of

The objective of this study was to determine whether a defect in mitochondrial respiratory function accompanies the development of diabetic cardiomyopathy. The hypothesis tested in this study is that a decrease in Ca2+ uptake into mitochondria may prevent the stimulation of Ca(2+)-sensitive matrix dehydrogenases and the rate of ATP synthesis. Streptozotocin (55 mg/kg)-induced diabetic rats were used as a model of insulin-dependent diabetes mellitus. Hearts from 4-wk diabetic rats had basal heart rates and rates of contraction and relaxation similar to control. Isoproterenol caused a similar increase in the rate of contraction in diabetic and control hearts, whereas the peak rate of relaxation was reduced in diabetic hearts. Mitochondrial Ca2+ uptake was reduced in mitochondria from diabetic hearts after 2 wk of diabetes. Na(+)-induced Ca2+ release was unchanged. State 3 respiration rate was depressed in mitochondria from diabetic rats only when the respiration was supported by the substrate of a Ca(2+)-regulated matrix enzyme. The pyruvate dehydrogenase activity was reduced in diabetic mitochondria compared with that of control. It was concluded that mitochondria from diabetic hearts had a decreased capacity to upregulate ATP synthesis via stimulation of Ca(2+)-sensitive matrix dehydrogenases. The impairment in the augmentation of ATP synthesis rate accompanies a decreased rate of relaxation during increased work load.

Effects of cesium on spontaneous rate in right atria isolated from diabetic rats

1993 ◽  
Vol 71 (9) ◽  
pp. 675-678 ◽  
Author(s):  
Richard H. Kennedy ◽  
Kristine K. Hicks ◽  
Joseph R. Stimers ◽  
Ernst Seifen
Keyword(s):  
Insulin Dependent Diabetes Mellitus ◽  
Diabetic Rats ◽  
Right Atrial ◽  
Dependent Diabetes Mellitus ◽  
Chronotropic Response ◽  
Spontaneous Rate ◽  
Insulin Dependent ◽  
Beating Rate ◽  
And Control ◽  
Right Atria

Previous studies have shown that streptozotocin (STZ) induced diabetes in rats is associated with a decrease in the spontaneous rate of isolated right atria. Present experiments were designed to determine whether this model of insulin-dependent diabetes mellitus alters the chronotropic actions of cesium (Cs+). Right atrial preparations were isolated from STZ-treated and diluent-treated control rats, and bathed in Krebs–Henseleit buffer at 37 °C; dose-dependent (0.2–10 mM) effects of Cs+ were examined by cumulative addition. Preparations isolated from diabetic rats had a slower beating rate before exposure to Cs+, and the negative chronotropic response to this cation was diminished in these tissues. In fact, at concentrations between 2 and 10 mM Cs+, spontaneous rate did not differ between the diabetic and control groups. These data suggest that the hyperpolarization-activated current, If, may play a role in the slower spontaneous pacemaker rate observed in right atria isolated from STZ-induced diabetic rats.Key words: cesium, heart rate, hyperpolarization-activated inward current, streptozotocin.

scholarly journals FTIR Spectroscopic Investigation of Mineral Structure of Streptozotocin Induced Diabetic Rat Femur and Tibia

2003 ◽  
Vol 17 (2-3) ◽  
pp. 627-633 ◽  
Author(s):  
Handan Boyar ◽  
Belma Turan ◽  
Feride Severcan
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Rat ◽  
Carbonate Content ◽  
Diabetic Patients ◽  
Type I ◽  
Mineral Density ◽  
Insulin Dependent

Diabetes mellitus (DM) can be accepted as a heterogenous multi organ disorder that can affect various systems of the human body. Disorders include retinopathy, neuropathy, cardiomyopathy, musculoskeletal abnormalities such as diminished bone formation and bone healing retardation. Low bone mineral density is often mentioned as a complication for patients with insulin dependent diabetes mellitus (type I DM). Streptozotocin (STZ) induced diabetic rats are good models for investigation of the complications of insulin dependent diabetes. In the present study, the effects of STZ induced diabetes on the mineral environment of rat bones namely femur and tibia were studied by Fourier transform infrared (FTIR) spectroscopic technique. The results revealed that mineral crystal sizes increased and carbonate content decreased for diabetic femur and tibia. These changes can be due to the formation of osteoporosis which is widely seen in diabetic patients.

Increased activity of the hexosamine synthesis pathway in muscles of insulin-resistant ob/ob mice

1997 ◽  
Vol 272 (6) ◽  
pp. E1080-E1088 ◽  
Author(s):  
M. G. Buse ◽  
K. A. Robinson ◽  
T. W. Gettys ◽  
E. G. McMahon ◽  
E. A. Gulve
Keyword(s):  
Insulin Resistance ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Hexosamine Biosynthetic Pathway ◽  
Insulin Resistant ◽  
Hindlimb Muscles ◽  
Glucose Flux ◽  
Hexosamine Pathway ◽  
Insulin Dependent ◽  
And Control

Enhanced glucose flux via the hexosamine biosynthetic pathway has been implicated in insulin resistance. We measured products of this pathway, UDP-N-acetyl hexosamines (UDP-HexNAc), and activity of the rate-limiting enzyme L-glutamine:D-fructose-6-phosphate amidotransferase (GFAT) in tissues of ob/ob mice and lean controls. Ob/ob mice were obese, hyperglycemic, and hyperinsulinemic. Resistance to the effect of insulin on glucose transport was demonstrated in isolated soleus muscles, although total GLUT-4 concentration was mildly increased in muscles from ob/ob mice. UDP-HexNAc concentrations in hindlimb muscles decreased between 8 and 17 wk but were always higher in ob/ob vs. controls (P < 0.001, mean increase 67%). Concentrations of UDP-hexoses and GDP-mannose were similar in ob/ob and control muscles. Muscle GFAT activity declined with age but was increased in ob/ob vs. controls at each age examined (P < 0.001, mean increase 108%). UDP-HexNAc concentrations and GFAT activity were similar in livers of ob/ob and controls. These data suggest that glucose flux via the hexosamine pathway is selectively increased in muscle but not liver of ob/ob mice and may contribute to muscle insulin resistance in this model of non-insulin-dependent diabetes mellitus.

Endothelial-dependent vasodilation is preserved in non-insulin-dependent Zucker fatty diabetic rats

1995 ◽  
Vol 268 (6) ◽  
pp. H2366-H2374 ◽  
Author(s):  
H. G. Bohlen ◽  
J. M. Lash
Keyword(s):  
Cell Function ◽  
Insulin Dependent Diabetes Mellitus ◽  
Diabetic Rats ◽  
Insulin Concentration ◽  
Dependent Diabetes Mellitus ◽  
Normal Male ◽  
Insulin Resistant ◽  
Release Of Acetylcholine ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic

Alterations in the structural properties of the microvasculature and in vasodilation mediated by endothelial- and, to some extent, nonendothelial-dependent mechanisms occurs in insulin-dependent diabetic humans and animals. Less severe problems of this type appear to occur during non-insulin-dependent diabetes mellitus (NIDDM) in humans, but data based on animal models of NIDDM are not available. The endothelial- and nonendothelial-mediated dilation of intestinal arterioles was studied in insulin-resistant male Zucker fatty diabetic (DB) rats and their lean normal male littermates (LM) at ages 22-25 and 35-40 wk. DB become hyperglycemic (450-550 mg/100 ml) at age 9-10 wk. Microiontophoretic release of acetylcholine, ADP, and nitroprusside onto arterioles caused equivalent dilation in LM and DB for both large and intermediate diameter arterioles. Administration of streptozotocin (STZ) to DB at age 18-19 wk lowered their insulin concentration approximately 25% but did not significantly effect the resting plasma glucose concentration. However, endothelial-dependent vasodilation was attenuated by 70-80% within 8-10 wk. The overall results indicate that prolonged hyperglycemia in insulin-resistant but hyperinsulinemic rats does not impair the endothelial- and nonendothelial-dependent dilation of the intestinal microvasculature. However, compromising beta-cell function with STZ, as indicated by lowering the insulin concentration by one-fourth, substantially compromises endothelial-dependent dilation similar to that found in insulin-dependent diabetic rats and humans.

Acute effect of calcium and insulin on hyperfiltration of early diabetes

1987 ◽  
Vol 252 (1) ◽  
pp. E13-E20 ◽  
Author(s):  
N. Bank ◽  
M. A. Lahorra ◽  
H. S. Aynedjian
Keyword(s):  
Diabetes Mellitus ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Filtration Rate ◽  
Insulin Dependent Diabetes Mellitus ◽  
Diabetic Rats ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent ◽  
Renal Vascular

We examined the effect of calcium administration on renal hyperfiltration in streptozotocin-treated diabetic rats. Rats were studied 7–10 days after streptozotocin injection. Intrarenal infusion of CaSO4 in Ringer's solution had no effect on the hyperfiltration of the diabetic kidney. Infusion of insulin in a dose that did not effect hyperglycemia also had no effect on the hyperfiltration. However, when insulin and calcium were infused together, a rapid decrease in glomerular filtration rate, single-nephron filtration rate, glomerular hydraulic pressure, and renal plasma flow occurred. The contralateral control kidney was unaffected. Verapamil infusion had no significant effect in untreated diabetic rats, but immediately reversed the vasoconstriction induced by insulin plus calcium. Similar intrarenal insulin and calcium infusions had no effect in euvolemic or chronically salt-loaded nondiabetic rats. The observations indicate that renal vascular cells (probably preglomerular) are hyperresponsive to calcium in early insulin-dependent diabetes mellitus and that this response requires insulin. We suggest that decreased renal vascular tone in early insulin-dependent diabetes mellitus may be due in part to defective transmembrane calcium flux across vascular smooth muscle cells. Insulin appears to be required for calcium entry or mobilization, to initiate renal vascular smooth muscle contraction in diabetes.

scholarly journals Diabetes with and without ketoacidosis on right atrial pacemaker rate and autonomic responsiveness

1997 ◽  
Vol 273 (4) ◽  
pp. H1888-H1893 ◽  
Author(s):  
Kristine K. Hicks ◽  
Ernst Seifen ◽  
Joseph R. Stimers ◽  
Richard H. Kennedy
Keyword(s):  
Insulin Dependent Diabetes Mellitus ◽  
Cholinergic Receptor ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
Right Atrial ◽  
Dependent Diabetes Mellitus ◽  
Half Maximal Effective Concentration ◽  
Insulin Dependent ◽  
Chronotropic Action ◽  
Right Atria

Experiments were designed to determine whether insulin-dependent diabetes mellitus (IDDM) alters direct chronotropic effects of adrenergic and cholinergic agonists and whether the observed changes are associated with hyperglycemia or combined hyperglycemia and ketoacidosis. Diabetes was induced by intravenous administration of 45, 50, or 65 mg/kg streptozotocin (STZ). Rats treated with 65 mg/kg STZ had higher levels of blood glucose and ketones compared with the levels of the other groups. Right atria were isolated 12 wk after administration of STZ and bathed in Krebs-Henseleit solution. Basal spontaneous pacemaker rate was diminished in preparations isolated from diabetic rats. The maximum pacemaker rate observed during exposure to isoproterenol or norepinephrine was also depressed in preparations from diabetic animals; however, the increase in rate and half-maximal effective concentration values for each agent were not affected. The sensitivity to the negative chronotropic action of acetylcholine was enhanced by IDDM, whereas the response to carbachol (a cholinergic agonist not readily metabolized by acetylcholinesterase) was not changed. No significant differences were observed when we compared preparations isolated from diabetic animals with and without ketoacidosis. In summary, these data suggest 1) that IDDM is associated with a diminished basal spontaneous pacemaker without changes in the responsiveness to adrenergic and cholinergic receptor activation and 2) that ketoacidosis does not play a role in the observed alterations.

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