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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic osteopenia has been known as one of the chronic complications of diabetes mellitus, and a decrease in bone turnover has been thought to be one of the pathophysiological characteristics of this complication. In order to investigate the effect of long-term insulin therapy on low bone turnover in diabetes, pancreas transplantation was performed on streptozotocin-induced diabetic rats. Plasma levels of bone gamma-carboxyglutamic acid-containing protein(osteocalcin) in untreated diabetic rats were 0.9 +/- 0.1 (mean +/- SEM) nmol/l, significantly lower than the value of 4.2 +/- 0.6 nmol/l in control rats (p less than 0.01). Pancreas transplantation reversed this decrease to 6.3 +/- 1.1 nmol/l, which was not significantly different from the value in control rats. The circulating levels of calcitriol were significantly decreased in the untreated diabetic group (p less than 0.01), and the decrease was fully reversed by pancreas transplantation. In addition, the decreases in bone length, strength and weight were also improved by the transplantation. This evidence clearly shows that the improvement of metabolic derangements in diabetes by insulin is essential for the prevention of deterioration in diabetic osteopenia. It is possible, therefore, that insulin exerts an indirect beneficial influence through the metabolic amelioration on the decreases in bone turnover and circulating osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the osteoblasts via the insulin receptor since its presence has been shown recently in osteoblastic cells.
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PMID:Effect of pancreas transplantation on decreased levels of circulating bone gamma-carboxyglutamic acid-containing protein and osteopenia in rats with streptozotocin-induced diabetes. 138 56

Alterations in the vascular bed of the pancreas or disturbances of the blood coagulation system are mostly considered to be sequelae of acute pancreatitis, but it seems that impairment of the pancreatic blood supply can per se lead to acute hemorrhagic pancreatitis. To test this hypothesis with a new animal model, we injected 20 microns polystyrene microspheres retrogradely into the distal splenic artery of rats, thus incompletely blocking blood perfusion in the splenic portion of the pancreas. Eight of eight rats (100%) subjected to microsphere injection developed acute hemorrhagic pancreatitis by 27 h after surgery, when they were killed, but none of the six sham-operated control animals (0%) showed macroscopic signs of pancreatitis. Blood amylase levels at death were 3,087 +/- 650 I.U./L (mean +/- SEM) and the histologic severity score for pancreatitis was 10.8 +/- 1.0 (mean +/- SEM), whereas in the six control rats amylase levels were 1,375 +/- 158 I.U./L and the histology score was only 1.7 +/- 1.0. The result is, with p less than 0.0005, highly significant (chi 2 analysis) and shows that acute experimental pancreatitis can indeed be induced by partially blocking the arterial blood supply within the organ.
Pancreas 1990 Mar
PMID:Injection of microspheres into pancreatic arteries causes acute hemorrhagic pancreatitis in the rat: a new animal model. 231 95

The present study was done to determine interaction of ethanol and marginal zinc nutriture on morphology and function of rat pancreas. Sprague-Dawley rats were maintained on Wayne Rodent-Blox ad libitum; marginal zinc-deficient diet plus ethanol ad libitum and pair fed with animals fed marginal zinc-deficient liquid diet and zinc-supplemented liquid diet with ethanol for 33 (+/- 1 SEM) days. Body, pancreas, liver, heart, and kidney weights were determined, and studies of pancreatic DNA, RNA, total proteins and newly labeled proteins, amylase, lipase, trypsinogen, and chymotrypsinogen were done on pancreatic lobules in vitro. Ethanol feeding independent of the zinc content of the diet caused a decrease in zinc content of the liver, body weight, liver and pancreas weight, pancreatic DNA, total protein, and amylase concentration and an increase in lipase and trypsinogen concentrations and in secretion of amylase and lipase. Interaction of the marginal zinc diet and ethanol feeding resulted in a decreased synthesis of RNA and secretion of newly synthesized protein and an increase in secretion of serine proteases. Morphological studies revealed a reduction in the number of zymogen granules in animals fed low levels of zinc, also with an accumulation of lipid droplets when the diet contained ethanol. These studies confirmed our previous observations of specific injury to the pancreas due to marginal zinc nutriture or to ethanol, independent of each other. Marginal zinc nutriture in concert with ethanol resulted in impaired RNA synthesis and secretion of nascent proteins and increased secretion of serine proteases. These data indicate that altered zinc metabolism induced by ethanol per se may contribute to ethanol-induced disturbance of pancreatic function.
Pancreas 1986
PMID:Interaction between marginal zinc deficiency and chronic alcoholism: pancreatic structure and function in rats in vitro. 243 69

Pancreas obtained from 34 adult human cadaver organ donors was divided into proximal and distal segments, and the duct to each segment was cannulated. Collagenase was injected into the proximal duct of 7 glands and into the distal duct of 7 others; the duct of the opposite segment was perfused with collagenase. The pancreas was then dispersed by teasing, trituration, and passage through filters. Perfused proximal and distal segments released 1461 +/- 287 and 2728 +/- 797 islets/g (+/- SEM) versus 710 +/- 149 (P less than 0.05) and 1950 +/- 636 after injection. Twenty other pancreases were perfused with collagenase warmed rapidly to 39 degrees C (n = 4) or warmed slowly to 37 degrees C (n = 6) or 39 degrees C (n = 10): the yield was 1625 +/- 632, 1320 +/- 116, and 2009 +/- 277 islets/g respectively. Total yields from the latter were 76 X 10(3) large (greater than 100 microns) and 85 X 10(3) small (less than 100 microns) islets with recoveries of 61% and 42%, respectively, after Ficoll density gradient purification. Histology showed highly purified islets. Perifusion with glucose elicited a biphasic release of insulin with the mean response (microU/islet/min) rising to a first peak of 0.5 and constant second phase secretion of 0.25, followed by a return to baseline. Reduced response was observed for islets from pancreas stored greater than 6 hr and tissue obtained from multiple centers. Less insulin was produced by freshly isolated islets, islets less than 100 microns, and after Ficoll separation. Secretion was similar for islets derived from proximal or distal segments. Perfusion of collagenase via the ducts of human pancreas improves islet isolation and Ficoll gradient separation yields highly purified islets. Important factors influencing insulin secretion are the source of donor tissue, cold storage of pancreas, Ficoll purification, islet size, and tissue culture.
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PMID:Studies of the isolation and viability of human islets of Langerhans. 283 43

In order to investigate the action of somatostatin-28 (SS-28) on the metabolic homeostasis of insulin-dependent diabetics, we compared its effects to those of somatostatin-14 (SS-14) in terms of insulin sparing, changes in dextrose demands, glucose fluctuations and behavior of growth hormone and glucagon secretion. Eight insulin-dependent subjects were connected to Artificial Endocrine Pancreas (Biostator) for 84 hours during which they received intravenous infusions of either SS-14, SS-28 or isotonic saline in a randomized order, after a steady state of metabolism had been achieved. Five of the patients received SS-28 100 micrograms/h and SS-14 250 micrograms/h for 10 hours and three of them SS-28, 50 micrograms/h and SS-14 250 micrograms/h for 12 hours. Identical doses of both peptides were administered as bolus infusions prior to the continuous ones. Under SS-28 100 micrograms/h and SS-14 250 micrograms/h patients required 13.5 +/- 2.3 and 14.5 +/- 1.9 U of insulin respectively vs 40 +/- 5.6 U under isotonic saline infusion (mean +/- SEM, P less than 0.005 and P less than 0.01). At the same period the apparatus delivered 15 times more dextrose under SS-28 and 20 times more under SS-14. The magnitude of glucose fluctuations diminished from 64.6 +/- 2.47 mg% without to 41.4 +/- 2 mg% under SS-14 (P less than 0.01) and 46 +/- 3.8 mg% under SS-28 (P less than 0.02). Similar changes were observed in the remaining three patients who received SS-28 in the dose of 50 micrograms/h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antidiabetic action of somatostatin-28 as assessed by the artificial endocrine pancreas: greater potency than somatostatin-14. 289 70

To examine whether plasma and urine concentrations of human atrial natriuretic peptide (hANP) are altered in patients with diabetes mellitus (DM), plasma and urine hANP concentrations were evaluated in 86 patients with diabetes mellitus using an extraction procedure. The mean recovery rate of extraction was 71.8 +/- 0.6% (mean +/- SEM). The major immunoreactive component of hANP in extracted plasma and urine appeared to be identical to synthetic alpha hANP as judged by reverse-phase high-performance liquid chromatography (HPLC). The patients were divided into three groups according to their renal complications. The patients in group 1 had no apparent abnormality in serum creatinine, serum or urine beta 2-microglobulin (beta 2-MG), or urine N-acetyl-beta-D-glucosaminidase (NAG); those in group 2 showed either beta 2-MG or NAG abnormality but no creatinine abnormality. The patients in group 3 were though to have an established diabetic nephropathy and showed a serum creatinine increase. Plasma ANP concentrations in groups 1, 2, and 3 were 10.7 +/- 2.1, 19.9 +/- 5.6, and 39.2 +/- 9.9 fmol/ml, respectively. These values in groups 2 and 3 were significantly higher than the control values (p less than 0.05 or p less than 0.01 versus 6.2 +/- 0.7 fmol/ml). Urine ANP concentrations in group 1 were also within normal range, though those in groups 2 and 3 markedly increased in comparison with normal values.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1988
PMID:Plasma and urine concentrations of atrial natriuretic peptide in patients with diabetes mellitus. 297 69

We have observed effects of acute hyperinsulinaemia on arterial pressure of five diabetics and tested the reproducibility of this action. Systolic (TAS) and diastolic (TAD) arterial pressure were studied during two hyperinsulinaemic-euglycaemic clamps effected with Artificial Pancreas (Biostator CGIIS, Miles) at one month of interval. During the first clamp, between the beginning of insulin infusion and the end of 4th stage, we have observed a fall of TAS (115 +/- 4, VS 137 +/- 6 mmHg; moy +/- SEM; p less than 0.05) and in less degree of TAD (76 +/- 2, VS 86 +/- 4 mmHg; NS). These modifications of arterial pressure were associated with no changes of heart rate and urinary sodium flow. On the other hand, we have observed a fall of serum levels of sodium (139 +/- 1, VS 141 +/- 1 mEq/l; p less than 0.05), urea (0.20 +/- 0.01, VS 0.32 +/- 0.02 g/l; p less than 0.001) whereas, balance-sheet of water was positive (+445 +/- 338 ml) at the end of clamp. During the second clamp, the fall of pressure has been reproducible, relating to the TAS (123 +/- 5, VS 145 +/- 4 mmHg; p less than 0.01) and non significantly to the TAD (78 +/- 2, VS 88 +/- 5 mmHg; NS). During the two tests, the mean of tension fall was identical (22 +/- 6 mmHg during first clamp, 22 +/- 4 mmHg during second one). So, acute hyperinsulinaemia induces a fall of arterial pressure, probably in bringing an influence on arterial vasodilatation since heart rate and urinary sodium excretion are unchanged and water balance-sheet is positive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Influence of acute hyperinsulinism on arterial pressure of diabetics. Reproducibility of the hypotensive effect]. 314 34

Postprandial serum glucose concentrations are determined by both the rates of glucose appearance and disposal in normal subjects and diabetic patients. The significance of each parameter following mixed meal remains controversial. We have compared the serum glucose and C-peptide responses, as well as glucose fluxes (D[3-3H]glucose technique), after a breakfast mixed meal in type II diabetic patients (n = 6) and normal subjects (n = 7). The mean (+/- SEM) fasting serum glucose and postprandial glycemic responses were significantly (p less than 0.001) higher in the diabetic patients compared with the normal subjects. Mean fasting serum C-peptide levels were similar in both groups. After the mixed meal ingestion, serum C-peptide levels were significantly higher at 20 min (p less than 0.02) and 40 min (p less than 0.01) in the normal subjects compared with diabetic patients. The mean basal hepatic glucose output was 124 +/- 15 vs. 70 +/- 6 mg/m2 min (p less than 0.001) in the diabetics compared with the normal subjects, respectively. After mixed meal ingestion, the incremental integrated areas and rates of splanchnic glucose appearance (RA) and utilization (RU) were significantly (p less than 0.001) higher in the diabetics versus normal subjects. Both basal and post-meal metabolic clearance rate (MCR) were significantly (p less than 0.05) lower in the diabetic patients when compared with the normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1987
PMID:The role of splanchnic glucose output in determining glycemic responses after mixed meal in type II diabetic patients and normal subjects. 362 36

Pancreas, double-fixed in glutaraldehyde and osmium tetroxide and embedded in epoxy resin was cut into sections 0.5-1 micron thick. The sections were surface-etched in an oxygen plasma produced by exciting oxygen with a radio frequency generator. Structural components of exocrine and endocrine cells were morphologically investigated in the secondary electron image mode of the SEM. Moreover, in order to identify some cell components such as endocrine granules, the morphological image obtained of the etched surface by the SEM were compared with those seen in a TEM, using the serial sections from the same tissue block and at the same cellular level. For a microanalytical investigation, tissues were fixed with glutaraldehyde alone. The structural components of exocrine and endocrine cells were analyzed by SEM/EDX. A better resolution under the SEM was obtained of 0.5-0.8 micron thick sections after surface-etching in an oxygen plasma for 1 minute. Intracellular structures such as nuclear membranes, nucleolus, mitochondria, rough endoplasmic reticulum and zymogen granules were readily identifiable. Moreover, the internal structure of organelles such as cristae of mitochondria was recognized. In the serial sections, the mode of arrangement of intracellular structures in the SEM was well consistent with those in the TEM. The peaks of phosphorus, sulphur and calcium were clearly detected from the intracellular components such as nucleolus, nuclear membranes and secretory granules.
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PMID:Scanning electron microscopy and EDX analysis of exocrine and endocrine gland cells of rat pancreas surface-etched in an oxygen plasma. 676 46

Trypsinogen activation peptide (TAP) concentration and alpha 2-macroglobulin-trypsin complex (alpha 2M-T) activity were measured in two experimental models of acute pancreatitis in rats to evaluate the significance of activation of trypsinogen in acute pancreatitis. TAP concentration and alpha 2M-T activity in serum rose significantly in trypsin-taurocholate-induced hemorrhagic acute pancreatitis, while in cerulein-induced edematous acute pancreatitis they did not rise in spite of a similar increase in immunoreactive trypsin. When rats in trypsin-taurocholate-induced pancreatitis were treated by protease inhibitor (FUT-175; nafamostat mesilate; FUT group), alpha 2M-T activity in serum was significantly lower than that in nontreated controls (mean +/- SEM, 20.8 +/- 1.43 U/L in the FUT group vs 79.1 +/- 24.5 in controls; p < 0.01). The survival rate at 24 h was significantly improved in the FUT group compared with the controls (70 vs 43%; p < 0.05). The increase in TAP concentration in the FUT group was similar to that in controls. The TAP concentration in pancreatic tissue at 24 h was significantly (p < 0.01) lower in the survival group (7.8 +/- 0.8 ng/ml) than in the lethal group (25.9 +/- 3.7 ng/ml). Activation of trypsinogen and its subsequent enzyme activity play an important role in the evolution of severe acute pancreatitis.
Pancreas 1995 Apr
PMID:Activation of trypsinogen in experimental models of acute pancreatitis in rats. 754 73


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