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E Adeghate

Publications and source records attributed to E Adeghate.

At least 19 recordsLinked to original sources

Effects of insulin treatment on heart rhythm, body temperature and physical activity in streptozotocin-induced diabetic rat.

1. Streptozotocin (STZ)-induced diabetic cardiomyopathy is frequently associated with depressed diastolic/systolic function and altered heart rhythm. 2. The effects of insulin treatment on heart rhythm, body temperature and physical activity in STZ-induced diabetic rats were investigated using biotelemetry techniques. 3. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar - Lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded with a telemetry system for 10 days before STZ treatment, for 20 days following administration of STZ (60 mg/kg) and thereafter, for 30 days while rats received daily insulin. 4. Heart rate, physical activity and body temperature declined rapidly 3-5 days after administration of STZ. Pre-STZ heart rate was 362 +/- 7 b.p.m., falling to 266 +/- 12 b.p.m. 5-15 days after STZ with significant recovery to 303 +/- 14 b.p.m. 10-20 days after commencement of insulin. Pre-STZ body temperature was 37.5 +/- 0.1C, falling to 37.2 +/- 0.2C 5-15 days after STZ with significant recovery to 37.5 +/- 0.1C 10-20 days after commencement of insulin. Physical activity and heart rate variability were also reduced after STZ but there was no significant recovery during insulin replacement. 5. Defective autonomic regulation and/or mechanisms of control that are intrinsic to the heart may underlie disturbances in heart rhythm in the STZ-induced diabetic rat.

Animals↗

Effect of high-calorie diet on the prevalence of diabetes mellitus in the one-humped camel (Camelus dromedarius).

The one-humped camel is a typical desert animal. It has the capability of withstanding the harsh climatic changes and the scarcity of food and water, in addition to the high-ambient temperature. The prevalence of diabetes mellitus in two different groups of the one-humped camel, group (A) control (n = 102) camels and group (B) high-calorie diet-fed camels (n = 103), in Al-Ain region (UAE) was studied using biochemical and radioimmunoassay techniques. In this article, 7% of the control camels have diabetes mellitus (blood glucose level: > or =140 mg/dL) compared to 21% of the high-calorie-fed camels. Plasma insulin level was significantly (P < 0.05) lower in group B compared to group A. The low insulin level in camels consuming high-caloric diet could be a sign of exhaustion of pancreatic beta cells. The hematological parameters were nearly similar in both groups and no significant differences were seen. Liver and kidney enzymes were normal in both groups. Iron and copper were significantly (P < 0.005) higher in the high-calorie-fed camels compared with the control. Our study indicates that high-caloric feed consumption in camels is associated with the development of disorders in glucose metabolism leading to diabetes mellitus.

Animals↗

Long-term effects of streptozotocin-induced diabetes on the electrocardiogram, physical activity and body temperature in rats.

In vivo biotelemetry studies have demonstrated that short-term streptozotocin (STZ)-induced diabetes is associated with a reduction in heart rate (HR) and heart rate variability (HRV) and prolongation of QT and QRS intervals. This study investigates the long-term effects of STZ-induced diabetes on the electrocardiogram (ECG), physical activity and body temperature. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. ECG, physical activity and body temperature data were continuously recorded with a telemetry system before and following the administration of STZ (60 mg kg(-1)) for a period of 22 weeks. HR, physical activity and body temperature declined rapidly 3-5 days after the administration of STZ. The effects became conspicuous with time reaching a new steady state approximately 1-2 weeks after STZ treatment. HR at 4 weeks was 268 +/- 5 beats min(-1) in diabetic rats compared to 347 +/- 12 beats min(-1) in age-matched controls. HRV at 4 weeks was also significantly reduced after STZ treatment (18 +/- 3 beats min(-1)) compared to controls (33 +/- 3 beats min(-1)). HR and HRV were not additionally altered in either diabetic rats (266 +/- 5 and 20 +/- 4 beats min(-1)) or age-matched controls (316 +/- 6 and 25 +/- 4 beats min(-1)) at 22 weeks. Reduced physical activity and/or body temperature may partly underlie the reductions in HR and HRV. In addition, the increased power spectral low frequency/high frequency ratio from 4 weeks after STZ treatment may indicate an accompanying disturbance in sympathovagal balance.

Animals↗

Immunohistochemical localization of orexin-B, orexin-1 receptor, ghrelin, GHS-R in the lacrimal gland of normal and diabetic rats.

Orexin-B, ghrelin and their receptors play an important role in the regulation of feeding in mammals. The pattern of distribution of orexin-B, orexin-1-receptor (OX1R), ghrelin and growth hormone secretagogue receptor (GHS-R) in the lacrimal gland of normal and diabetic rats has not been reported. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) at 60 mg kg(-1). Forty weeks after the induction of STZ-induced diabetes, normal, age-matched controls and diabetic rats were anesthetized with chloral hydrate (intraperitoneally) and their lacrimal glands removed and processed for immunofluorescence. Orexin-B was observed in the cells localized to the interacinar regions while OX1R was discerned in the nerves innervating the wall of small blood vessels. Ghrelin was also present in a group of cells located in the periacinar regions of the lacrimal glands of normal and diabetic rats. In contrast, GHS-R was observed in the apical region of the ductal cells of the lacrimal glands of both normal and diabetic rats. The pattern of distribution of these orexigenic peptides and their receptors did not significantly change after the onset of diabetes. In conclusion, orexin-B, ghrelin and their receptors are present in the lacrimal glands of both normal and diabetic rats and may play a role in the regulation of lacrimal gland function.

Animals↗

Short-term effects of streptozotocin-induced diabetes on the electrocardiogram, physical activity and body temperature in rats.

A variety of contractility defects have been reported in the streptozotocin (STZ)-induced diabetic rat heart including alterations to the amplitude and time course of cardiac muscle contraction. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. Electrocardiogram (ECG), physical activity and body temperature data were continuously recorded with a telemetry system before and following the administration of STZ (60 mg kg-1). Heart rate (HR), physical activity and body temperature declined rapidly 3-5 days after administration of STZ. The effects became more conspicuous with time and reached a new steady state approximately 10 days after STZ treatment when HR was 255+/-8 beats min-1 in diabetic rats compared to 348+/-17 beats min-1 in age-matched controls. Heart rate variability (HRV) was also significantly reduced after STZ treatment (18+/-3 beats min-1) compared to controls (36+/-3 beats min-1). Reduced physical activity and/or body temperature may partly underlie the reduction in HR and HRV. Reductions in power spectral density at higher frequencies (2.5-3.5 Hz) suggest that parasympathetic drive to the heart may be altered during the early stages of STZ-induced diabetes. Short-term diabetes-induced changes in vital signs can be effectively tracked by continuous recording using a telemetry system.

Animals↗

The progressive effects of a fat enriched diet on ventricular myocyte contraction and intracellular Ca2+ in the C57BL/6J mouse.

The C57BL/6J mouse has a genetic susceptibility to develop diabetes when fed with a high-fat, high-sucrose diet. The general characteristics of diet-induced diabetes in this model include progressive development of hyperinsulinaemia, hyperglycaemia, insulin resistance and obesity, features that are frequently observed in the clinical setting. This study investigated the progressive effects of a fat enriched (FE) diet on contraction and intracellular Ca2+ in ventricular myocytes from the C57BL/6J mouse. The characteristics of the mice fed with the FE diet compared to mice receiving control diet included progressive increase in the rate of body weight gain, increased fasting blood glucose and time-dependent differences in the disposal of blood glucose after a glucose challenge. The ultrastructure of cardiac myocytes and associated capillaries did not show any gross morphological alteration after 27 weeks of FE diet compared to controls. At 5 months the resting cell length (RCL) and the kinetics of shortening were not significantly altered in ventricular myocytes from mice receiving the FE diet compared to age-matched controls. At 5 and at 7 months the amplitude of shortening was increased in myocytes receiving the FED diet compared to controls. At 7 months the time to half (THALF) relaxation of myocyte contraction was shortened in myocytes from mice receiving the FE diet compared to controls. Mean THALF relaxation in myocytes from mice fed the FE diet was 32.0 +/- 1.4 ms (n = 23) compared to 40.2 +/- 2.0 ms (n = 27) in controls. Neither resting intracellular Ca+ nor the kinetics or amplitude of the Ca2+ transient were altered by FE diet. Differences in myofilament sensitivity to Ca2+ might underlie the changes in contractility.

Animals↗

Subchronic exposure to high-dose ACE-inhibitor moexipril induces catalase activity in rat liver.

The long-term clinical effects of ACE-inhibitors have similarities with those of both fibrates and glitazones, activators of peroxisome proliferator activator receptor (PPAR) alpha and gamma, respectively. The antioxidant enzyme catalase, a heme protein that degrades hydrogen peroxide, is found at high concentrations in peroxisomes. Catalase activity is one of the recognized surrogate markers indicative of PPAR activation in the rat liver. The purpose of the study was to establish the effect of moexipril on catalase activity and to compare it with the effect of both saline controls and that of the known PPAR agonist clofibrate (positive control). Three groups of seven rats were used. All substances were applied i.p. daily for 5 days, followed by a 2-day break. The cycle was repeated eight times. After the final cycle (day 56) the animals were sacrificed and liver tissue collected. The number of catalase positive cells in both moexipril group (95% CI 57-61) and clofibrate group (95% CI 72-80) is higher than in controls (95% CI 3-16) (p < or = 0.01). The number of catalase positive cells in the clofibrate group is higher than in the moexipril group (p < or = 0.01). High-dose subchronic exposure to the ACE-inhibitor moexipril induces catalase activity in the rat liver to an extent comparable to fibrates. We suggest that some of the long-term advantages of ACE inhibitor use - beyond mere BP lowering - might be due to a PPAR mediated effect.

Angiotensin-Converting Enzyme Inhibitors↗

An update on the biology and physiology of resistin.

Resistin is a newly discovered adipocyte hormone. It is related to resistin-like molecules alpha, beta and gamma in structure and function. Resistin is produced by white and brown adipose tissues but has also has been identified in several other tissues, including the hypothalamus, pituitary and adrenal glands, pancreas, gastrointestinal tract, myocytes, spleen, white blood cells and plasma. The tissue level of resistin is decreased by insulin, cytokines such as tumour necrosis factor alpha, endothelin-1 and increased by growth and gonadal hormones, hyperglycaemia, male gender and some proinflammatory cytokines, such as interleukin-6 and lipopolysaccharide. Resistin antagonizes insulin action, and it is downregulated by rosiglitazone and peroxisome proliferator-activated receptor gamma agonists. Since evidence of a direct link between resistin genotype and human diabetes is still weak, more molecular, physiological and clinical studies are needed to determine the role of resistin in the aetiology of type 2 diabetes.

Adipose Tissue↗

Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat.

This study investigated the beneficial effects and mechanism of action of the juice of Momordica charantia in streptozotocin (STZ)-induced diabetes mellitus in rats. Diabetes mellitus was associated with significant (p < 0.01) time course reductions in body weight, plasma insulin and the number of insulin positive cells per islet and significant (p < 0.01) time course elevation in blood glucose and osmolarity and systolic blood pressure compared to age-matched healthy controls. Oral intake of M. charantia juice by STZ-induced diabetic rats partially reversed all the diabetes-induced effects measured. Daily oral administration of M. charantia juice to STZ-induced diabetic rates significantly (p < 0.01) reduced the Na+- and K+-dependent absorptions of glucose by the brush border membrane vesicles of the jejunum compared to the responses obtained in STZ-induced diabetic rat. Either insulin (100 MM) or the fruit juice lyophilised extract (5 microg x ml(-1)) can stimulate 14C-D-glucose uptake in L6 myotubes. These effects were completely blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase. High concentrations (10-200 microg x ml(-1)) of M. charantia juice extract inhibited 14C-D-glucose uptake in L6 myotubes compared to the control response. The effect of M. charantia treatment was also investigated on myelinated fibre abnormalities in the tibial nerve of STZ-induced diabetic and control rats. The results show that diabetes was associated with significant (p < 0.05) reduction in the mean cross-sectional myelinated nerve fibres, axonal area, myelin area and maximal fibre area compared to end controls. Treatment of STZ-induced diabetic rats with M. charantia juice normalised the structural abnormalities of peripheral nerves. The results indicate that M. charantia can exert marked beneficial effects in diabetic rats, and moreover, it can regulate glucose uptake into jejunum membrane brush border vesicles and stimulate glucose uptake into skeletal muscle cells similar to the response obtained with insulin.

Animals↗

Momordica charantia fruit juice stimulates glucose and amino acid uptakes in L6 myotubes.

The fruit of Momordica charantia (family: Cucurbitacea) is used widely as a hypoglycaemic agent to treat diabetes mellitus (DM). The mechanism of the hypoglycaemic action of M. charantia in vitro is not fully understood. This study investigated the effect of M. charantia juice on either 3H-2-deoxyglucose or N-methyl-amino-a-isobutyric acid (14C-Me-AIB) uptake in L6 rat muscle cells cultured to the myotube stage. The fresh juice was centrifuged at 5000 rpm and the supernatant lyophilised. L6 myotubes were incubated with either insulin (100 nM), different concentrations (1-10 microg ml(-1)) of the juice or its chloroform extract or wortmannin (100 nM) over a period of 1- 6 h. The results were expressed as pmol min(-1) (mg cell protein)(-1), n = 6-8 for each value. Basal 3H-deoxyglucose and 14C-Me-AIB uptakes by L6 myotubes after 1 h of incubation were (means +/- S.E.M.) 32.14 +/- 1.34 and 13.48 +/- 1.86 pmol min(-1) (mg cell protein)(-1), respectively. Incubation of L6 myotubes with 100 nM insulin for 1 h resulted in significant (ANOVA, p < 0.05) increases in 3H-deoxyglucose and 14C-Me-AIB uptakes. Typically, 3H-deoxyglucose and 14C-Me-AIB uptakes in the presence of insulin were 58.57 +/- 4.49 and 29.52 +/- 3.41 pmol min(-1) (mg cell protein(-1)), respectively. Incubation of L6 myotubes with three different concentrations (1, 5 and 10 microg ml(-1)) of either the lyophilised juice or its chloroform extract resulted in time-dependent increases in 3H-deoxy-D-glucose and 14C-Me-AIB uptakes, with maximal uptakes occurring at a concentration of 5 microg ml(-1). Incubation of either insulin or the juice in the presence of wortmannin (a phosphatidylinositol 3-kinase inhibitor) resulted in a marked inhibition of 3H-deoxyglucose by L6 myotubes compared to the uptake obtained with either insulin or the juice alone. The results indicate that M. charantia fruit juice acts like insulin to exert its hypoglycaemic effect and moreover, it can stimulate amino acid uptake into skeletal muscle cells just like insulin.

Amino Acids↗

Streptozotocin-induced type 1 diabetes mellitus alters the morphology, secretory function and acyl lipid contents in the isolated rat parotid salivary gland.

Diabetes mellitus (DM) is associated with numerous conditions including hypo-secretion of digestive enzymes. This study investigated the morphology, secretory function (alpha-amylase release) and acyl lipid contents in the isolated parotid gland of STZ-induced diabetic and age-matched control rats in order to provide insights into diabetes-induced salivary insufficiency. The techniques employed included light microscopy, colourimetric and gas chromatography (GC) analysis, respectively. Diabetes mellitus was induced in adult male Wistar rats by a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg per kg body weight). Control animals were injected with a similar volume of citrate buffer. The animals were tested for DM 4 days after STZ injection and 2 months later when they were humanely killed for the experiment. The morphological results showed diabetic parotid glands to be extensively infiltrated with lipid droplets of various magnitudes, whereas glands from control animals display normal structure with the absence of lipid droplets. The analysis of parotid secretory function revealed a significant (p < 0.05) dose-dependent decrease in alpha-amylase release in response to noradrenaline (NA) in STZ-treated glands when compared to age-match control parotid glands. Furthermore, the levels of acyl lipids (16:0, 16:1, 18:0 and 18:1) in diabetic parotid glands was significantly (p < 0.01) reduced compared to control glands, along with a reduced ratio of 16:1/16:0. The results indicate DM can elicit changes in the morphology, secretory function and acyl fatty acid quantity in the isolated rat parotid gland.

Age Factors↗

Increase in neuronal nitric oxide synthase content of the gastroduodenal tract of diabetic rats.

This study examined the changes occurring in the pattern of distribution and expression of neuronal nitric oxide synthase (nNOS)-positive nerves in the gastroduodenal tract of streptozotocin-induced diabetic rats. The ganglion cells of the myenteric plexus of the gastric antrum of normal rats contain nNOS. We also observed nNOS-positive neurons and fibres in the myenteric plexus of the duodenum of normal rats. After the onset of diabetes, the number and intensity of staining of nNOS-positive nerve profiles in the gastric antrum and duodenum did not change significantly. However, Western blotting showed a significant increase in the expression of nNOS after the onset of diabetes. In conclusion, diabetes of 4 and 32 weeks duration induced an increase in the tissue content of nNOS in the gastroduodenum of rat. The increase in the level of nNOS in the gastroduodenum of diabetic rats may explain why impaired gastric emptying is common in patients with diabetes.

Animals↗

Ghrelin stimulates insulin secretion from the pancreas of normal and diabetic rats.

Ghrelin is a novel 28-amino acid gut-brain peptide, which was first isolated in the rat stomach. This study examined the effect of ghrelin on insulin secretion from the isolated pancreas of normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin. Four weeks after the induction of diabetes, pancreatic tissue fragments of normal and diabetic rats were treated with different concentrations (10(-12), 10(-9) and 10(-6) M) of ghrelin. Ghrelin evoked large and significant increases in insulin secretion from the pancreas of both normal and diabetic rats. In the pancreas of normal rats, diltiazem (calcium channel antagonist) or a combination of atropine (muscarinic cholinergic receptor antagonist), propranolol (beta-adrenergic receptor antagonist) and yohimbine (alpha2-adrenergic receptor antagonist) significantly reduced the stimulatory effect of ghrelin on insulin secretion. Diltiazem and yohimbine failed to inhibit ghrelin-evoked insulin release in diabetic rat pancreas. Ghrelin-immunoreactivity cells was observed in 2.6% and 3.8% of the total cell population in the islet of Langerhans of normal and diabetic rats, respectively.

Adrenergic alpha-Antagonists↗

GABA in the endocrine pancreas: cellular localization and function in normal and diabetic rats.

Gamma amino butyric acid (GABA) and its related enzymes have been demonstrated in pancreatic beta cells of normal rat. Antibodies against GABA-synthesizing enzymes have been implicated in the pathogenesis of Type I diabetes. In spite of the importance of GABA in the aetiology of diabetes mellitus, detailed morphological data on the pattern of distribution of GABA in the pancreas of normal and diabetic rats are lacking. Diabetes mellitus (DM) was induced by a single dose of streptozotocin (STZ) given intraperitoneally (60 mg kg body weight(-1)). Four weeks after the induction of DM, normal (n = 6) and diabetic (n = 6) rats were anesthetized with chloral hydrate and their pancreata were removed and processed for the localization and effect of GABA on insulin secretion using immunohistochemistry and radioimmunoassay techniques. The number of GABA-like immunoreactive (GABA-LIR) cells in the pancreatic islets of STZ-diabetic rats decreased significantly (P<0.0001) when compared to non-diabetic control rats. The pattern and percentage distribution of GABA in the islet of Langerhans of normal and diabetic rat was similar to that of insulin. GABA induced a significant (P<0.0007) increase in insulin secretion from the pancreas of normal rats. In diabetic pancreas, GABA evoked a higher but not significant (P<0.1) increase in insulin secretion. These findings showed that the number of GABA-LIR cells is reduced significantly in diabetes. Moreover, GABA is a strong secretagogue of insulin from the pancreas of normal rat.

Animals↗

L-arginine stimulates insulin secretion from the pancreas of normal and diabetic rats.

Several reports have shown that nitric oxide (NO) stimulates glucose-induced insulin secretion in the pancreas of normal rat but the effect of L-arginine (a NO donor) on insulin secretion from the pancreas of diabetic pancreas is unknown. Fragments of pancreatic tissue from normal and diabetic rats were incubated for 45 min in Krebs solution containing 100mM L-arginine. The supernatant was subsequently analyzed for the insulin content using radioimmunoassay technique. L-arginine evoked large increases in insulin secretion from the pancreas of diabetic rat. The insulin secreted from the pancreas of diabetic rat was numerically but not significantly lower compared to that of normal rat pancreas. In conclusion, L-arginine, a nitric oxide donor stimulates insulin secretion from the pancreas of diabetic rats.

Animals↗

Distribution of vasoactive intestinal polypeptide, neuropeptide-Y and substance P and their effects on insulin secretion from the in vitro pancreas of normal and diabetic rats.

This study examined the pattern of distribution of vasoactive intestinal polypeptide (VIP), neuropeptide-Y (NPY) and substance P (SP) in the pancreas of diabetic rat to determine whether there are changes in the number and pattern of distribution of these neuropeptides after the onset of diabetes. Moreover, the effect of VIP, NPY and SP on insulin secretion from the pancreas of normal and diabetic rats was also examined. Diabetes mellitus (DM) was induced by a single dose of streptozotocin (STZ) given intraperitoneally (i.p.) (60 mg kg body weight(-1)). Four weeks after the induction of DM, diabetic (n = 6) and normal (n = 6) rats were anesthetized with chloral hydrate and their pancreases removed and processed for immunohistochemistry and insulin secretion. The number of insulin-positive cells in the islets of Langerhans was reduced while that of VIP and NPY increased significantly after the onset of diabetes. The pattern of distribution of VIP, NPY and SP in the nerves innervating the pancreas was similar in both normal and diabetic rats. VIP-evoked large and significant (P < 0.02) increases in insulin secretion from the pancreas of normal and diabetic rats. NPY also induced a marked (P < 0.005) increase in insulin release from pancreatic tissue fragments of normal rat. Stimulation of pancreatic tissue fragments of diabetic rat with NPY resulted in a slight but not significant increase in insulin release. SP induced a large and significant (P < 0.005) increase in insulin secretion from the pancreas of normal rat but inhibited insulin secretion significantly (P < 0.03) from isolated pancreas of diabetic rat. In summary, VIP and NPY can stimulate insulin secretion from the pancreas after the onset of diabetes. The stimulatory effect of SP on insulin secretion is reversed to inhibitory in diabetic rats.

Animals↗

Large reduction in the number of galanin-immunoreactive cells in pancreatic islets of diabetic rats.

Although galanin has been shown to be present in pancreatic islet cells, there is no literature available on the pattern of distribution and the effect of galanin in the pancreas of diabetic animals or human models. The aim of this study was to examine whether galanin immunoreactivity changes after the onset of diabetes mellitus in the rat model. The present study used immunohistochemical techniques to examine the pattern of distribution of galanin-like immunoreactive cells in the pancreas of rats with streptozotocin-induced diabetes. The effect of galanin on insulin secretion from intact rat pancreatic tissue fragments was also investigated using a radioimmunoassay technique. Numerous galanin-like immunoreactive cells were observed in both the peripheral and central regions of the islet of Langerhans of normal rat pancreas. By contrast, the islets of diabetic rat pancreas contained significantly (P < 0.0001) fewer galanin-like immunoreactive cells than nondiabetic rats. Galanin was colocalized with insulin in the islets of normal and diabetic rats. Galanin had an inhibitory effect on insulin secretion from the isolated pancreatic tissue fragments of normal and diabetic rats at all concentrations (10(-12) to 10(-6) M) employed. Galanin at 10(-9) M caused a significant (P < 0.02) decrease in insulin secretion from normal rat pancreatic tissue fragments compared to basal. These observations indicate that galanin may play a significant role in the regulation of insulin secretion.

Animals↗