Loss of sensitivity to cholecystokinin stimulation of isolated pancreatic acini from genetically diabetic rats

1995 ◽  
Vol 268 (3) ◽  
pp. E531-E536 ◽  
Author(s):  
M. Otsuki ◽  
T. Akiyama ◽  
H. Shirohara ◽  
S. Nakano ◽  
K. Furumi ◽  
...  
Keyword(s):  
Serum Glucose ◽  
Diabetic Rats ◽  
Exocrine Function ◽  
Guanine Nucleotide Binding Protein ◽  
Rat Serum ◽  
Pancreatic Acini ◽  
Isolated Pancreatic Acini ◽  
Long Evans ◽  
Oletf Rat

Pancreatic exocrine function of a new inbred strain Otsuka Long-Evans Tokushima Fatty (OLETF) rat that develops spontaneous persistent hyperglycemia was evaluated in in vitro isolated pancreatic acini and compared with that in the control Long-Evans Tokushima Otsuka (LETO) rat. Serum glucose and insulin concentrations in the OLETF rats were significantly high (glucose: 270 +/- 12 vs. 208 +/- 10 mg/100 ml, P < 0.01; insulin: 12.4 +/- 1.7 vs. 4.9 +/- 0.6 ng/ml, P) < 0.01), whereas pancreatic wet weight was significantly low (803 +/- 20 vs. 1,138 +/- 17 mg, P < 0.01) compared with those in the LETO rat. Pancreatic acini isolated from the OLETF rat were totally insensitive to cholecystokinin (CCK)-8 stimulation at concentrations of up to 100 nM. However, neither the responsiveness nor the sensitivity to carbamylcholine, bombesin, and secretin of the acini from the OLETF rat was altered or even increased, probably due to the larger amylase content in the OLETF rat acini compared with those of the LETO rat acini (31.5 +/- 2.0 vs. 13.0 +/- 1.1 Somogyi units/micrograms DNA, P < 0.01). The responsiveness to fluoride, a direct activator of guanine nucleotide-binding protein, in the OLETF rat acini was similar to that in the LETO rat, suggesting that the transmembrane signaling and effectors and subsequent intracellular signal transduction molecules in the OLETF rat acini are normal. Moreover, 125I-CCK binding to the acini prepared from the OLETF rat was totally absent. These present results indicate that the OLETF rat has a selective defect in the binding of CCK to its receptors on the acinar cell surface.

Altered release of growth hormone from dispersed adenohypophysial cells of streptozotocin diabetic rats. I. Effects of growth hormone releasing factor and somatostatin

1989 ◽  
Vol 67 (10) ◽  
pp. 1315-1320 ◽  
Author(s):  
M. S. Sheppard ◽  
B. A. Eatock ◽  
R. M. Bala
Keyword(s):  
Growth Hormone ◽  
Early Morning ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Hormone Release ◽  
Growth Hormone Release ◽  
Growth Hormone Releasing Factor ◽  
Rat Growth ◽  
Streptozotocin Diabetic Rats

As growth hormone has been implicated in the "dawn phenomenon," an early morning rise in serum glucose, we have studied the control of growth hormone release in diabetes using an acutely dispersed system of adenohypophysial cells from normal or diabetic rats (65 mg/kg streptozotocin, 8 days before sacrifice; serum glucose, 490 ± 17 mg/dL). Growth hormone release is normally controlled by the two hypothalamic hormones, growth hormone releasing factor and somatostatin. We have found cells of the diabetic rats exhibit changes in sensitivity that result in increased growth hormone release in static incubation. In normal cells, rat growth hormone releasing factor increases growth hormone release three- to four-fold with an EC50 of 151 ± 27 pM (n = 7). In contrast, in cells from diabetic rats, there was a significant (twofold) increase in sensitivity to growth hormone releasing factor (EC50 = 75 ± 15 pM, n = 7) which resulted in increased growth hormone release with lower but not maximal (10 nM) growth hormone releasing factor. Basal nonstimulated release was unchanged. Somatostatin inhibition of stimulated growth hormone release was reduced (n = 7); half-maximal inhibition occurred with 0.21 ± 0.03 nM (normal) and 0.76 ± 0.17 nM somatotatin (diabetic). In perifusion the peak secretion rate was significantly lower for diabetic cells stimulated by a maximal dose of growth hormone releasing factor. These studies suggest somatotrophs of diabetic rats have altered sensitivity in vitro to the controlling hormones growth hormone releasing factor and somatostatin.Key words: growth hormone, diabetes, streptozotocin, growth hormone releasing factor, somatostatin.

scholarly journals Enhanced proteolytic activity directed against the N-terminal of IGF-I in diabetic rats

1999 ◽  
Vol 162 (2) ◽  
pp. 243-250 ◽  
Author(s):  
H Yamamoto ◽  
C Maake ◽  
LJ Murphy
Keyword(s):  
Protease Activity ◽  
Insulin Treatment ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Acute Administration ◽  
Mrna Levels ◽  
Igf I ◽  
Streptozotocin Diabetic Rats ◽  
Biotin Label

We have recently identified in serum an acid protease which is capable of generating des(1-3)IGF-I from intact IGF-I. Here we have utilized a synthetic substrate with the sequence, biotin-G-P-E-T-L-C-BSA which contains the N-terminal sequence of IGF-I, to investigate the levels of this protease activity in streptozotocin-diabetic rats. Protease activity, quantified in terms of the amount of the biotin label lost, was determined in serum and hepatic extracts from normal control rats, diabetic rats and insulin-treated diabetic rats. Both the serum protease activity and protease activity in hepatic extracts were significantly increased in diabetic rats compared with control rats (P<0.02 and P<0.005). Following acute administration of insulin, a rapid and marked reduction in serum protease activity was observed; with an approximately 50% reduction apparent at 30 min (P<0.001). Chronic insulin treatment of diabetic rats also significantly reduced the serum and hepatic protease activity to the levels seen in control rats. A positive correlation between protease activity and serum glucose level was observed (r=0.58, P<0.005). The abundance of Spi 2.1 mRNA, a serine protease inhibitor, capable of inhibiting the IGF-I protease activity in vitro, was significantly decreased in the liver of diabetic rats and insulin treatment of diabetic rats did not normalize Spi 2.1 mRNA levels. These data suggest that the conversion of IGF-I to the more active des(1-3)IGF-I variant may be enhanced in diabetic animals. Since serum IGF-I levels are reduced in diabetic rats, increased des(1-3)IGF-I-generating protease activity would enhance the functional activity of the circulating IGF-I.

Effect of lanthanum on pancreatic protein synthesis in streptozotocin-diabetic rats

1983 ◽  
Vol 244 (3) ◽  
pp. G321-G326
Author(s):  
M. Korc
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Diabetic Rats ◽  
Cell Membrane Permeability ◽  
Exocrine Function ◽  
Amino Acid Incorporation ◽  
Pancreatic Acini ◽  
Acid Incorporation ◽  
Enhance Protein Synthesis ◽  
Streptozotocin Diabetic Rats

The role of extracellular Ca2+ in mediating the stimulatory effect of cholecystokinin octapeptide (CCK8) on [3H]phenylalanine incorporation into protein was studied in isolated pancreatic acini from streptozotocin-diabetic rats. The stimulatory effect of CCK8 (10(-10) M) on [3H]phenylalanine incorporation was completely abolished by preincubating acini with either 10(-4) M lanthanum or 10(-3) M manganese. At these concentrations neither compound altered the basal rate of amino acid incorporation, and both compounds inhibited CCK-mediated Ca2+ influx without affecting either basal or CCK-mediated 45Ca2+ efflux. Lanthanum (10(-4) M) also blocked the stimulatory effect of the cholinergic analogue carbachol (10(-5) M) on amino acid incorporation but did not alter the stimulatory effect of insulin (1.67 x 10(-8) M). Vasoactive intestinal polypeptide and 12-O-tetradecanoyl-phorbol-13-acetate failed to increase the incorporation of [3H]phenylalanine into acinar protein. These findings suggest that CCK and other pancreatic secretagogues that act via Ca2+ enhance protein synthesis by increasing cell membrane permeability to Ca2+ and provide additional evidence that this may be an important mechanism by which CCK regulates pancreatic exocrine function.

scholarly journals Effects of secretagogues on [32P]phosphatidylinositol 4,5-bisphosphate metabolism in the exocrine pancreas

1983 ◽  
Vol 212 (2) ◽  
pp. 483-488 ◽  
Author(s):  
J W Putney ◽  
G M Burgess ◽  
S P Halenda ◽  
J S McKinney ◽  
R P Rubin
Keyword(s):  
Exocrine Pancreas ◽  
Secretory Response ◽  
Isolated Cells ◽  
Early Step ◽  
Pancreatic Acini ◽  
Isolated Pancreatic Acini ◽  
Stimulus Response ◽  
Phosphatidylinositol 4 ◽  
Similar Decrease

Experiments were carried out to assess the effects of secretagogues on the polyphosphoinositides phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] on preparations of exocrine pancreas in vitro. Carbachol and caerulein provoked a rapid (less than 1 min) breakdown of 15-20% of [32P]PtdIns(4,5)P2 in isolated pancreatic acini, but did not affect [32P]PtdIns4P. In contrast, the Ca2+ ionophore ionomycin had no immediate effect on the levels of either inositide but caused a parallel fall in both lipids after 5-10 min. A similar decrease in [32P]PtdIns(4,5)P2 due to carbachol was obtained with isolated acini and isolated cells, despite the fact that the secretory response of isolated cells was considerably less than that of isolated acini. Loss of [32P]PtdIns(4,5)P2 elicited by carbachol or caerulein was unaffected either by the addition of EGTA in excess of extracellular Ca2+ or when a protocol was employed that eliminated caerulein-induced intracellular Ca2+-release. These results suggest that agonist-induced PtdIns(4,5)P2 breakdown in the exocrine pancreas may be an early step in the stimulus-response coupling pathway and also suggest that this breakdown is not dependent on Ca2+-mobilization.

Improved Large-Scale Isolation of Breeder Porcine Islets: Possibility of Harvesting from Nonheart-Beating Donor

1998 ◽  
Vol 7 (4) ◽  
pp. 397-402 ◽  
Author(s):  
Masaaki Miyamoto ◽  
Kazutomo Inoue ◽  
Yuanjun Gu ◽  
Thein Tun ◽  
Wanxing Cui ◽  
...  
Keyword(s):  
Large Scale ◽  
Total Yield ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Isolation Procedure ◽  
Ischemic Time ◽  
Glucose Levels ◽  
Porcine Islets ◽  
Dextran 70

To establish a large-scale isolation procedure for adult porcine islets usable as a donor source for xenotransplantation and as a model of human islet isolation, we improved several characteristics of the conventional isolation procedure. At a slaughterhouse we first selected a breeder pig over 1.5 years old (and over 200 kg in weight) with warm ischemic time (WIT) of 15 ± 2 minutes as nonheart-beating donors. Then, we made a special enzymic mixture that consisted of collagenase S-1 (260 U/mg, NittaZelatin, Japan), collagenase P (1.86 U/ml Lyo Boehringer-Mannheim, USA), DNase (Sigma, St. Louis, Mo), Disparse (NittaZelatin, Japan), and protease inhibitor (Sigma). Third, this mixture was injected very gently into the pancreatic duct at the time of pancreatic harvesting. To prevent overdigestion of the pancreas, the mixture was first cooled to less than 10°C. Fourth, during the warm digestion of pancreas, the pancreas with the enzymic mixture was quietly put in a water bath at 37°C without mechanical shaking. Fifth, we purified the islets with a COBE 2991 cell processor by the Dextran 70 gradient method, because Dextran 70 is very cheap and has the same purification effect as the Ficoll gradient. The results of 10 consecutive breeder porcine islet isolations are reported. The total yield of isolations of islets over 50 μm in the longest diameter after staining with Dithizone (DTZ) was 85,900 ± 19,954 islets, 291,667 ± 240,452 IEQ (2,900 ± 2,324 IEQ/g). The purity of the isolated islets was very high: 90.2 ± 3.8%. Glucose stimulation during in vitro incubation induced significant insulin release from isolated breeder porcine islets. In two of the diabetic rats receiving encapsulated islets grafts using a mesh-reinforced polyvinyl alcohol hydrogel bag (MRPB), a prominent reduction in serum glucose levels (less than 200 mg/dL) persisted for 13 and 19 days, respectively, after intraperitoneal xenotransplantation islets without immunosuppression. In conclusion, we succeeded in a more efficient and less-expensive isolation of a large amount of adult porcine islets from a nonheart-beating donor.

scholarly journals Antidiabetic Potential of Stem Bark Extract of Enantia chlorantha and Lack of Modulation of Its Therapeutic Efficacy in Diabetic Rats Co-Administered with Lisinopril

2021 ◽  
Vol 68 (1) ◽  
pp. 127-127
Author(s):  
Latifat Bolanle Ibrahim ◽  
Patience Funmilayo Idowu ◽  
Opemipo Adekanye Moses ◽  
Mutiu Adewunmi Alabi ◽  
Emmanuel Oladipo Ajani
Keyword(s):  
Lipid Profile ◽  
Stem Bark ◽  
Inhibitory Effect ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Bark Extract ◽  
Therapeutic Implications ◽  
Glucose Levels

This study validates the antidiabetic efficacy of Enantia chlorantha stem bark and the possible therapeutic implications of the co-administration of lisinopril and E. chlorantha in type 2 diabetic rats. E. chlorantha stem bark was extracted by cold maceration. The inhibitory effect of the plant on carbohydrate metabolizing enzymes and its antioxidative potentials were assessed in vitro. The extract exhibited α-amylase and α-glucosidase inhibitory activities and also showed antioxidative properties in vitro. Administration of the extract normalized fasting hyperglycemia in vivo by showing 47.24% reduction in blood glucose levels relative to untreated diabetic rats. Co-administration of E. chlorantha and lisinopril restored serum glucose and serum lipid profile levels. E. chlorantha stem bark displayed antidiabetic potentials as compared with a standard antidiabetic drug (metformin). The study also showed that the plant contained some bioactive compounds which we hypothesize might be responsible for the observed activities. Co-administration of the plant with lisinopril conferred no significant therapeutic advantage on the serum glucose level and lipid profile.

Flavonoids Extracted from Asteriscus graveolens Improve Glucose Metabo-lism and Lipid Profile in Diabetic Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Fadwa El-ouady ◽  
Fatima Bachir ◽  
Mohamed Eddouks
Keyword(s):  
Glucose Tolerance ◽  
Lipid Profile ◽  
Histopathological Examination ◽  
Oral Treatment ◽  
Hdl Cholesterol ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Traditional Use ◽  
Soxhlet Apparatus

Aim: This study aimed to evaluate the antidiabetic and antihyperlipidemic effects of Asteriscus graveolens. Background: Asteriscus graveolens (Asteraceae) is a medicinal plant widely used by the Moroccan population to treat various diseases including diabetes. Objective: This work aimed to assess the capacity of flavonoids extracted from Asteriscus graveolens (FEE) to improve diabetes mellitus and dyslipidemia in normal and STZ-induced diabetic rats. Methods: Flavonoids were extracted from A. graveolens using the Soxhlet apparatus and using different organic solvents. Normal and streptozotocin-induced diabetic rats were treated orally by the extract of A. graveolens at a dose of 10 mg/kg. The oral treatment during 15 days was used to evaluate the effect of the flavonoids extracted from A. graveolens on blood glucose level and lipid profile in normal and diabetic rats. The oral glucose tolerance test as well as the analysis of histopathological examination of liver was performed. The antioxidant activity of FEE was also assessed by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH), in order to estimate the mechanisms of action involved by FEE to improve hyperglycemia and lipid profile in normal and diabetic rats. Results: FEE reduced serum glucose concentrations in both normal and diabetic rats and exhibited in the last group lowering total cholesterol and triglycerides effects as well as improvement of the HDL-cholesterol serum level. In addition, a remarkable influence on glucose tolerance was also noticed after FEE treatment. Moreover, FEE was able to improve histopathological status of liver and possess a potential antioxidant effect in vitro. Conclusion: In conclusion, this study demonstrates the hypoglycemic and antihyperlipidemic effects of FEE in rats supporting then its traditional use for the management of diabetes.

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