Role of glucagon in intestinal hyperemia associated with early experimental diabetes mellitus

1988 ◽  
Vol 255 (5) ◽  
pp. G542-G546
Author(s):  
L. F. Yrle ◽  
J. K. Smith ◽  
J. N. Benoit ◽  
D. N. Granger ◽  
R. J. Korthuis

The role of glucagon as a blood-borne mediator of the intestinal hyperemia associated with experimental diabetes mellitus was assessed in anesthetized fasted (18-24 h) rats 4 wk after the administration of streptozotocin (65 mg/kg body wt) or its vehicle. Selective removal of pancreatic glucagon from the circulation was accomplished by the intravenous administration of a highly specific glucagon antiserum. Blood flow to the gastrointestinal tract and kidneys was measured with radioactive microspheres using the reference sample technique. Blood flows were increased by at least 60% in each segment of the gastrointestinal tract of diabetic animals compared with control rats. Glucagon antiserum had no effect on blood flows in the gastrointestinal tract of control animals. However, the antiserum produced a significant reduction in blood flow to the stomach (26%), duodenum (25%), jejunum (12%), and kidneys (16%) in diabetic rats. There was no change in blood flow to the ileum or colon of diabetic animals with antiserum administration. The results of this study support the hypothesis that glucagon mediates a portion of the hyperemia noted in the stomach, duodenum, and jejunum. However, glucagon does not appear to play a role in the genesis of the hyperemia noted in more distal segments of the gastrointestinal tract (ileum and colon). A possible role for glucagon in the maintenance of renal blood flow in diabetic rats is suggested.

1999 ◽  
Vol 277 (3) ◽  
pp. R725-R733 ◽  
Author(s):  
Axel C. Pflueger ◽  
Timothy S. Larson ◽  
Siegfried Hagl ◽  
Franklyn G. Knox

The role of nitric oxide (NO) in the regulation of the intrarenal microcirculation in streptozotocin (STZ)-induced diabetes mellitus in rats is not clear. We examined renal cortical and papillary hemodynamics in STZ rats and determined the effects of systemic inhibition and stimulation of NO synthesis. Renal blood flow in cortical (QCC), and inner medullary ascending (QAV) and descending (QDV) vasa recta capillaries was measured by fluorescence videomicroscopy in STZ Munich-Wistar rats and nondiabetic control rats. Ten days after STZ injection (80 mg/kg ip), basal QCC and QDV were significantly greater in STZ rats ( n = 16) compared with control rats ( n = 15). Infusion of N G-monomethyl-l-arginine (l-NMMA, 15 mg/kg bolus, 500 μg ⋅ min−1 ⋅ kg−1iv) decreased QCC (−41%), QAV (−38%), and QDV (−37%) in control rats ( n = 6) and to a significantly greater magnitude than in STZ rats ( n = 7), QCC (−14%), QAV (−20%), and QDV (−25%). Coinfusion ofl-arginine (l-Arg, 1 mg ⋅ kg−1 ⋅ min−1iv) with l-NMMA increased QCC to a significantly greater extent ( P < 0.01) in control rats compared with STZ rats. In subsequent studies, infusion ofl-Arg alone increased QCC (+50%), QAV (+16%), and QDV (+11%) in control rats ( n = 5) but had no effect in STZ rats ( n = 5). These results show that the response of renal cortical and papillary capillary blood flow to both inhibition and stimulation of NO synthesis is attenuated in the early onset of STZ-diabetes mellitus rats compared with control rats.


Author(s):  
Р.И. Айзман ◽  
А.П. Козлова ◽  
Е.И. Гордеева ◽  
М.С. Головин ◽  
Г.А. Корощенко ◽  
...  

Цель - исследование влияния куркумы длинной и галеги восточной на осмо- и ионорегулирующую функции почек крыс при аллоксан-индуцированном сахарном диабете и острой почечной недостаточности в эксперименте. Методика. Эксперименты выполнены на самцах крыс Wistar (n=70) с моделью сахарного диабета (1-я серия) и острой почечной недостаточности (2-я серия). В обеих сериях животные были поделены на 3 группы: крыс 1-й группы содержали на стандартном корме, крысам остальных групп в корм добавляли куркуму (2-я группа) или галегу (3-я группа) (2% от массы корма). На 7-е сут эксперимента проводили исследование диуретической и ионоуретической функций почек натощак и после 5% водной нагрузки. Концентрацию ионов в моче и плазме определяли методом пламенной фотометрии; осмотическую концентрацию биологических жидкостей - методом криоскопии; биохимические показатели крови - колориметрическим методом. Результаты. У животных с сахарным диабетом фоновый диурез, а также экскреция натрия и калия были статистически значимо выше, чем у контрольных животных. При острой почечной недостаточности наблюдался более низкий уровень диуреза и ионоуреза, особенно после водной нагрузки. Прием куркумы и галеги вызывал улучшение осмо- и ионорегулирующей функции почек у крыс с сахарным диабетом, и практически не влиял на эти функции почек при острой почечной недостаточности. Заключение. При сахарном диабете оба фитопрепарата вызывали понижение концентрации глюкозы, креатинина, мочевины и улучшение ионно-осмотических показателей плазмы крови, при этом эффект куркумы был выражен отчетливее. При острой почечной недостаточности эти фитопрепараты не давали описанного эффекта. Aim. To study effects of the phytomedicines, Curcuma longa and Galega orientalis, on osmosis- and ion-regulating renal functions in rats with experimental diabetes mellitus (DM) and acute renal failure (ARF). Methods. Experiments were performed in two series on Wistar male rats (n=70) with modeled diabetes mellitus (series 1) and acute renal failure (series 2). In each series, the animals were divided into 3 groups, 1) rats of group 1 receiving a standard diet; 2) rats of groups 2 and 3 receiving a standard diet supplemented with turmeric or galega (2% of food weight), respectively. On the 7th day of the experiment, the diuretic and ionuretic renal function was studied in fasting state and after 5% water loading. Concentrations of ions in urine and plasma were determined by flame photometry; osmotic concentrations of biological fluids were measured by cryoscopy; blood biochemical parameters were measured by colorimetry. Results. In diabetic rats, background diuresis and sodium and potassium excretion were significantly higher than in the control animals. In rats with acute renal failure, diuresis and ionuresis were significantly lower, particularly after the water loading. Turmeric and galega supplementation improved the osmotic and ion-regulating renal function in diabetic rats and left practically unchanged these functions in rats with acute renal failure. Conclusion. In rats with diabetes mellitus, both herbal remedies reduced concentrations of glucose, creatinine, and urea and improved ion-osmotic parameters of blood plasma with a more pronounced effect of turmeric. In acute renal failure, these phytomedicines did not produce the described effects.


1997 ◽  
Vol 273 (1) ◽  
pp. E164-E173 ◽  
Author(s):  
K. Chang ◽  
Y. Ido ◽  
W. LeJeune ◽  
J. R. Williamson ◽  
R. G. Tilton

Sciatic nerve blood flow in diabetic rats in typically increased or unchanged when assessed by the reference sample microsphere method in our laboratory. In contrast, blood flow is generally reported to be decreased approximately 50% when assessed with laser Doppler flowmetry or hydrogen clearance polarography. To address concerns that increased blood flow observed with microspheres might be anomalous because of their particulate nature and/or because insufficient numbers of microspheres are captured in the nerve, a plasma-soluble "molecular microsphere" ([3H]desmethylimipramine, mol wt = 266) and 11.3-micron 153Gd-labeled microspheres were injected sequentially to assess blood flow in rats with streptozotocin diabetes of 2-4 wk duration. Nerve blood flows in diabetic rats were increased 1.5- to 2-fold (vs. control rats) with both tracers; these increases were prevented by tolrestat, an inhibitor of aldose reductase. These observations indicate that blood flow in sciatic nerve (like that in retina and kidney) is increased early after the onset of diabetes and is 1) demonstrable with a plasma-soluble tracer as well as with particulate microspheres and 2) linked to increased metabolism of glucose via the sorbitol pathway.


1994 ◽  
Vol 267 (5) ◽  
pp. F816-F824 ◽  
Author(s):  
R. G. Marcus ◽  
R. England ◽  
K. Nguyen ◽  
M. J. Charron ◽  
J. P. Briggs ◽  
...  

Because the insulin-responsive glucose transporter, GLUT4, is expressed in renal vascular and glomerular cells, we determined the effects of experimental diabetes mellitus on GLUT4 expression and glucose uptake by these tissues. Quantitative reverse-transcription polymerase chain reaction studies of microdissected afferent microvessels and renal glomeruli showed that, after 1 wk of diabetes, GLUT4 mRNA was decreased to 26 and 34% of control values, respectively. GLUT4 immunoblots of renal glomerular and microvessel samples showed that GLUT4 polypeptide was decreased to 51% of control values. These results were confirmed by indirect immunofluorescence, which showed decreased GLUT4 expression in glomerular cells and in vascular smooth muscle cells of the afferent microvasculature of diabetic animals. Uptake of the glucose analogue, 2-deoxyglucose, was also depressed in microvessels of diabetic rats to 57% of control values, supporting the conclusion that fewer total glucose transporters were available for glucose uptake into diabetic renal glomerular and microvascular cells. Thus both GLUT4 expression and glucose uptake by glomerular and microvascular cells are decreased in diabetic animals. These results have led us to suggest a mechanism by which decreased renal GLUT4 expression could contribute to glomerular hyperfiltration and hypertension seen in early diabetes.


2002 ◽  
Vol 60 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Jacqueline Nelisis Zanoni ◽  
Luzmarina Hernandes ◽  
Roberto Barbosa Bazotte ◽  
Marcílio Hubner de Miranda Neto

The aim of this study was to evaluate the effect of the ascorbic acid (AA) supplementation on the neurons that produce the vasoactive intestinal peptide (VIP) in the submucous plexus of the ileum of rat, four months after the induction of experimental diabetes mellitus with streptozotocin. Three groups of rats were used: C - control, D - diabetic, DA - diabetic receiving AA. We have measured the immunoreactivity and area of 80 cellular bodies of VIP-ergic neurons from each studied group. In the diabetic animals, we have observed hyperphagia, polydipsia, and an increase of glycemia and glycated hemoglobin. The VIP-ergic neurons have presented an increase of their immunoreactivity and the highest profiles when compared to the other groups. In the diabetic animals supplemented with AA it has been observed a small reduction in the glycemia and the water and food intake. We have also noticed smaller immunoreactivity in their VIP-ergic neurons, similar to what we have observed in the control group animals (group C).


Life Sciences ◽  
2018 ◽  
Vol 200 ◽  
pp. 63-68 ◽  
Author(s):  
Jhohann Richard de Lima Benzi ◽  
Priscila Akemi Yamamoto ◽  
Jessica Hanna Stevens ◽  
Amanda Martins Baviera ◽  
Natália Valadares de Moraes

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