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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study tried to improve the number of viable islets isolated from a pancreas because a sufficient number cannot be obtained when the organ is preserved in the manner used for pancreas transplantation. The mechanism involved in the decrease in islet yield during preservation was studied to try to develop a better method for islet preparation. First, the integrity of the ductal system was compared between fresh and 6-hr simply preserved (in Hanks' balanced salt solution) rat pancreases. The ductal pressure after ductal injection of HBSS reached a plateau earlier and was significantly lower for the preserved pancreases (0.073 +/- 0.026 min, 410 +/- 17 mmHg, n = 5) than for the fresh ones (0.176 +/- 0.086 min, 561 +/- 103 mmHg, n = 7, P less than 0.05). Second, the extent of pancreatic distention was examined following ductal injection of barium gelatin solution. Solution leakage occurred earlier and distention was less in the preserved pancreas. In addition, the gelatin was found in the capillaries within some islets of the preserved pancreas. These results indicated that the preservation led to a rapid loss of integrity of the ductal system before collagenase injection. We therefore tested the efficacy of ductal collagenase injection at the time of harvesting: 15 ml of 1.0 mg/ml collagenase HBSS was intraductally injected and the pancreas was preserved at 4 degrees C for 2, 4, 6, and 24 hr. The isolation procedure was similar to that used for the fresh pancreas. The yield was significantly better than that of the simply preserved pancreas at 4 hr (241 +/- 22, n = 3, vs. 140 +/- 58, n = 3, P less than 0.05) and at 6 hr (171 +/- 58, n = 14, vs. 32 +/- 33, n = 6, P less than 0.01). These isolated islets were spherical-oval and their viability was confirmed by the ability to reverse STZ-induced diabetes in mice. These results indicated that the integrity of the ductal system, which is necessary for distention of the whole pancreas, was lost during preservation. To solve this problem, ductal collagenase injection should be done at the time of pancreas harvesting and then followed by simple preservation. This method is recommended to obtain viable islets from a preserved pancreas.
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PMID:Improvement in islet yield from a cold-preserved pancreas by pancreatic ductal collagenase distention at the time of harvesting. 184 29

Vanadate has been previously shown to normalize blood glucose in streptozotocin-induced diabetic (STZ-DM) rats. The effect of a previously studied dose of vanadate (0.8 mg/ml) in drinking water on blood glucose, renal hypertrophy, and whole kidney polyol accumulation was studied in STZ-DM rats. Rats with diabetes of 5 weeks duration had higher blood glucose, greater urinary output, higher kidney weight, lower body weight, and higher kidney to body weight ratios than controls. Whole kidney sorbitol concentrations were significantly increased in diabetes but myo-inositol levels were unchanged vs control animals. After four weeks of oral vanadate treatment, blood glucose, urine volume, and kidney weights were similar to control values. Kidney to body weight ratios fell below that of the STZ-DM animals, but because body weights remained decreased, the kidney to body weight ratios were not normalized. Renal sorbitol levels returned to control values and renal myo-inositol levels remained unchanged in STZ-DM and normal animals treated with vanadate. These results provide evidence that vanadate therapy may result in regression of the hypertrophy and polyol accumulation characteristic of diabetic nephropathy in STZ-DM rats. This effect is most likely due to normalization of blood glucose by the insulin-mimetic activity of vanadate treatment.
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PMID:Effect of vanadate on renal hypertrophy and sorbitol accumulation in streptozotocin induced diabetes in rats. 187 50

To assess the effect of chemical stimulation of the central nervous system (CNS) on ketogenesis, we injected neostigmine (5 x 10(-8)mol) into the third cerebral ventricle in normal rats fasted for 48 h and fed rats with diabetes induced by streptozotocin (STZ, 80 mg/kg). The hepatic venous plasma levels of ketone bodies (3-hydroxybutyrate and acetoacetate), free fatty acids (FFA), and glucose were measured for 120 min after the injection of neostigmine under pentobarbital anesthesia. In the normal rats, plasma glucose levels were significantly increased but neither ketone bodies nor FFA were affected by CNS stimulation with neostigmine. In contrast the plasma levels of ketone bodies and FFA were significantly increased in STZ-diabetic rats, while glucose levels remained unchanged. The intravenous infusion of somatostatin (1.0 microgram/kg/min) suppressed the increase in plasma ketone bodies following CNS stimulation in STZ-diabetic rats. These findings suggest that CNS stimulation with neostigmine may accelerate ketogenesis by promoting the lipolysis, which may be induced by glucagon, in fed diabetic rats but not in normal fasted rats.
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PMID:Reciprocal changes of plasma glucose and ketone bodies in fasted and acutely diabetic rats after CNS stimulation. 189 76

Previous studies indicate that experimental diabetic autonomic neuropathy can be largely prevented by initiating therapy at the onset of diabetes. More clinically relevant, however, is the ability of therapy to reverse established neuropathy produced by long-standing diabetes. We have examined the effect of selected therapies on established neuroaxonal dystrophy (NAD) in ileal mesenteric nerves, a rat model of diabetic autonomic neuropathy. Groups of 3-mo-old rats were made diabetic with streptozocin (STZ-D) and allowed to survive untreated for 5 mo, at which time they were begun on sorbinil, dietary myo-inositol, and daily insulin therapies or left untreated for an additional 2 or 4 mo. Ultrastructural evidence of NAD was demonstrated in ileal mesenteric nerves of rats with untreated 5-mo STZ-D and increased with the duration of diabetes. No lesions were demonstrated in control rats of any age. myo-Inositol or sorbinil administration failed to alter the severity of diabetes as measured by its metabolic indices. Institution of sorbinil or insulin treatment at 5 mo of diabetes prevented the increase in, but did not normalize, NAD at 7 or 9 mo. Dietary myo-inositol failed to significantly reverse established NAD or prevent its initial development. Morphometric examination of ileal mesenteric nerves demonstrated a decrease in the number of axons comprising each diabetic Schwann cell unit, suggestive of chronic cycles of axonal degeneration and regeneration. This parameter, clearly abnormal by 5 mo of diabetes, was not normalized by 2 or 4 mo of insulin, sorbinil, or myo-inositol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 May
PMID:Effects of sorbinil, dietary myo-inositol supplementation, and insulin on resolution of neuroaxonal dystrophy in mesenteric nerves of streptozocin-induced diabetic rats. 190 27

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) revealed a new mode of hypoglycemic action with a more rapid onset and a shorter duration of action than the sulfonylureas (SUs). Hypoglycemic mechanisms and glycemic control benefits were demonstrated in laboratory animals. The stimulatory effect of A-4166 on insulin release, in fasting dogs with a cannula into the portal vein, was more rapid than that of tolbutamide after oral administration. A-4166 stopped the stimulation of insulin secretion very quickly, whereas tolbutamide maintained an elevation in plasma insulin levels for at least 6 hours. In the case of A-4166, a counter-regulatory glucagon response was observed during recovery from hypoglycemia, but it was significantly inhibited by tolbutamide. Hyperglycemia induced by glucose loading was rapidly inhibited by A-4166 in normal rats, in genetically diabetic KK mice and in STZ-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. Also, repeated administration of A-4166 for 2 weeks enhanced insulin secretion in the same manner as a single administration in normal rats. In conclusion, A-4166 is a new type of oral hypoglycemic agent, having a rapid and short-term insulin secretory effect and no suppressive effect on the hypoglycemia-induced glucagon response. Oral therapy with A-4166 would be beneficial in supplementing endogenous insulin secretion and would exert ideal glycemic control in NIDDM patients.
Diabetes Res Clin Pract 1991 Apr
PMID:Possibility of ideal blood glucose control by a new oral hypoglycemic agent, N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166), and its stimulatory effect on insulin secretion in animals. 190 97

We have been stressing the advantage of stationary digestion because of its simplicity and reproducible high yields of viable islets. In the present study optimal conditions of stationary in vitro collagenase digestion in mice and rats were examined. We also compared two possible routes for collagenase injection; ductal (PD) and portal venous (PV) based on subsequent islet yield and ability to reverse diabetes in rats. Three parameters which affect the quality of digestion are 1) collagenase concentration, 2) incubation time and 3) digestion temperature. Suitable conditions were easily determined and reproducible high yield of islets could be consistently obtained. The islets from one mouse pancreas (approximately 200 islets) could consistently restore normoglycemia in one STZ-induced diabetic mouse and the islets from one rat pancreas (500-600 islets) can restore normoglycemia in 5-6 STZ-induced diabetic mice within a couple of days. Islet yield in the PD method was greater than that in the PV method, and insulin release from PD islets in response to high glucose was well preserved after 24 hours of culture when compared to PV islets. The ability to restore normoglycemia in STZ-induced diabetic mice was well preserved when transplanting 100 PD islets as compared with the same number of PV islets. The PD islets revealed a well preserved structure with healthy endocrine cells, while the PV islets showed a dilated capillary network and distorted endocrine cell continuity. Histological examination of digested tissue following PD injection showed the complete destruction of pancreatic exocrine tissue, as well as mechanical separation and digestion of interstitial tissue between the islets and exocrine tissue, with the islet being preserved selectively intact.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Crucial role of pancreatic ductal collagenase injection for isolation of pancreatic islets. 196 78

The ability of insulin replacement to reverse the adverse effects of streptozocin-induced diabetes (STZ-D) on neuroendocrine and sexual function was tested in adult male rats. Rats were injected with STZ (50 mg/kg) or vehicle and then either started immediately on insulin (continuous) or allowed to remain untreated for 4 wk before insulin replacement was started (delayed). Replacement consisted of 5 IU/kg of insulin injected just before the lights were turned off and 2 IU/kg of insulin injected within 1 h of the lights being turned on. Copulatory behavior was tested 2, 4, 5, and 6 wk after induction of diabetes. Forty-five days after STZ administration, rats were killed for measurement of plasma hormone levels and hypothalamic catecholamine turnover and serotonin content. The STZ-D rats showed significant deficits in mount, intromission, and ejaculatory behaviors that were prevented by continuous insulin replacement. Delayed insulin replacement reversed the deficits in mount and intromission behaviors but not ejaculatory behavior. Plasma luteinizing hormone levels were unaffected by STZ or insulin treatment, but plasma testosterone and prolactin levels were both reduced in the diabetic animals. Continuous or delayed insulin replacement normalized both testosterone and prolactin levels. Median eminence, medial basal hypothalamus, anterior hypothalamus, and olfactory bulb rates of norepinephrine turnover were all reduced after STZ administration. Delayed insulin replacement restored norepinephrine turnover in all brain regions, whereas continuous insulin replacement enhanced norepinephrine turnover in the anterior hypothalamus and olfactory bulb but only partially blocked the effects of STZ in the median eminence and medial basal hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Aug
PMID:Effect of continuous versus delayed insulin replacement on sex behavior and neuroendocrine function in diabetic male rats. 197 72

To assess the role of the central nervous system (CNS) in carbohydrate metabolism in diabetes, neostigmine was injected into the third cerebral ventricle in fed rats with streptozotocin (STZ; 80 mg/kg)-induced diabetes under pentobarbital sodium anesthesia. Changes in hepatic venous plasma glucose concentrations were monitored. Neostigmine injection caused no significant changes in the hepatic venous plasma glucose concentration in untreated diabetic rats, whereas the glucose level increased significantly in insulin-treated diabetic rats similarly to the changes in normal control animals. In diabetic rats, the plasma levels of glucagon, epinephrine, and norepinephrine were increased significantly by neostigmine. After various doses (35-80 mg/kg) were given to rats, it was found that the higher the STZ dose, the lower was the hepatic glycogen content and the smaller was the glycemic response to neostigmine. Our results indicate that, in severe diabetes, CNS stimulation with neostigmine fails to increase hepatic glucose output, because glycogen stores are nearly exhausted and gluconeogenesis is already maximal.
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PMID:CNS stimulation does not affect hepatic venous glucose concentration in severely diabetic rats. 200 97

The streptozocin-induced diabetic (STZ-D) mouse was found to be a suitable model for studying the effects of maternal diabetes on the preimplantation embryo. This study looked at the effects of maternal diabetes on embryonic growth. Female Quakenbush mice were made diabetic (plasma glucose levels greater than 20 mM) by injection of 190 mg/kg i.p. STZ and were superovulated by standard methods. The blastocysts collected on day 4 from diabetic mothers had 8.5% fewer cells and a 35% lower protein synthetic rate than control embryos. Their cellular protein synthetic rate was 19% less than that in controls. Morulae from diabetic mothers also displayed a reduced protein synthetic rate, but this reduction was not seen in the two-cell embryo. Furthermore, blastocysts cultured in vitro from two-cell embryos from diabetic and control mothers displayed similar protein synthetic rates. This infers that the two-cell embryos from diabetic mothers are normal, and the retardation seen in later development in vivo occurs after the two-cell stage while the embryo is still free in the oviductal and uterine environment. Treatment of the diabetic mice with ultralente insulin every 12 h raised the protein synthetic rate of those blastocysts toward control levels, whereas treatment with lente insulin every 8 h recovered the embryo to the same rate as the control embryos. Because insulin has been shown to be mitogenic and stimulates protein synthesis of morulae and blastocysts in vitro, the absence of insulin in the diabetic mothers may be the cause of the retardation observed in their preimplantation embryos.
Diabetes 1991 Apr
PMID:Maternal diabetes and retarded preimplantation development of mice. 201 45

Diabetes has been reported to impair vasodilatory responses in the peripheral vascular tissue. However, little is known about vasodilatory function in the diabetic brain. We therefore studied, in the N2O-sedated, paralyzed, and artificially ventilated rat, the effects of chronic hyperglycemic diabetes on the cerebral blood flow (CBF) responses to 3 acutely imposed vasodilatory stimuli: hypoglycemia (HG) (plasma glucose = 1.6-1.9 mumol ml-1), hypoxia (HX) (PaO2 = 35-38 mm Hg), or hypercarbia HC) (PaCO2 = 75-78 mm Hg). In addition, we evaluated the somatosensory evoked potential (SSEP) and plasma catecholamine changes in rats exposed to acute glycemic reductions. Diabetes was induced via streptozotocin (STZ, 60 mg kg-1 i.p.). All results in diabetic rats were compared to those obtained in age-matched nondiabetic controls. The animals were studied at 6-8 weeks (HG experiments) or 4-6 months (HG, HX, and HC experiments) post-STZ. Values for CBF were obtained for the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) employing radiolabeled microspheres. Up to three CBF determinations were made in each animal. In 6-8 week diabetics vs. controls, CBF increased to a lesser value in the CX, SC, and BS (p less than 0.05). Thus, in the diabetics, going from chronic hyperglycemia to acute hypoglycemia, CBF values (in ml 100 g-1 min-1 +/- SD) increased (p less than 0.05) from 89 +/- 22 to 221 +/- 57 in the CX, from 82 +/- 21 to 160 +/- 52 in the SC, and from 79 +/- 34 to 237 +/- 125 in the BS. In controls, going from normoglycemia to acute hypoglycemia, the CBF changes (p less than 0.05) were 128 +/- 27 to 350 +/- 219 (CX), 117 +/- 11 to 358 +/- 206 (SC), and 130 +/- 29 to 452 +/- 254 (BS). CBF changes and absolute values in the CE were similar in the two groups. At 4-6 months post-STZ, a complete loss of the hypoglycemic CBF response was found in the CX, SC, and CE. In the BS, a CBF response to hypoglycemia was seen in the diabetic rats, with the CBF increasing from 114 +/- 28 (hyperglycemia) to 270 +/- 204 ml 100 g-1 min-1 (p less than 0.05), compared to a change from 147 +/- 36 (normoglycemia) to 455 +/- 299 ml 100 g-1 min-1 (p less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic hyperglycemic diabetes in the rat is associated with a selective impairment of cerebral vasodilatory responses. 205 Jul 55


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