Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of streptozocin-induced diabetes on Ca2+ fluxes and intracellular free-Ca2+ [( Ca2+]i) levels were studied in isolated rat pancreatic acini. The basal rates of 45Ca influx in acini and of 45Ca efflux from acini that were preloaded with 45Ca were similar in normal and diabetic rats. The gastrointestinal hormone cholecystokinin octapeptide (CCK-8, 0.1 nM) and the Ca2+ ionophore A23187 (2 microM) increased 45Ca influx to the same extent in both groups of acini. CCK-8 and the divalent cation manganese exerted marked stimulatory effects on 45Ca efflux. In contrast to the rapid effect of CCK-8 on 45Ca efflux, the effect of manganese was slow in onset and was greater in diabetic rat acini. The diabetic state was also associated with a significant decrease in resting [Ca2+]i levels, as determined with the Ca2+ indicator quin 2. Furthermore, the ability of CCK-8 to raise [Ca2+]i levels was significantly attenuated in these cells. Insulin did not alter either basal or CCK-8-mediated increases in [Ca2+]i levels. Our findings suggest that insulin deficiency is associated with multiple alterations in Ca2+ homeostasis in the pancreatic acinar cell. These include a decrease in basal [Ca2+]i levels, perturbations in the signal transduction system that mediates the rapid mobilization of [Ca2+]i after CCK-8-receptor binding, and enhanced sensitivity to the actions of manganese on intracellular Ca2+ pools.
Diabetes 1988 Jan
PMID:Quin 2 and manganese define multiple alterations in cellular calcium homeostasis in diabetic rat pancreas. 312 14

Isolated pancreatic acini from streptozocin-induced diabetic rats were used to study the role of insulin on the synthesis of specific cellular proteins. When acini were incubated with 0-100 nM insulin for 2 h and then pulsed with [35S]methionine, a dose-dependent increase in [35S]methionine incorporation into total cellular proteins was observed. When acinar cell lysates were subjected to gel electrophoresis, 12 major newly synthesized protein bands were resolved. Insulin (100 nM) increased the incorporation of [35S]methionine into all bands but with significantly different rates, varying from 84 to 216% of control. Next, specific antibodies to amylase, trypsin, ribonuclease, myosin, and lactate dehydrogenase (LDH) were used to evaluate the biosynthesis of known proteins. Insulin stimulated labeled amino acid incorporation into amylase by 148% over control. Insulin stimulated the synthesis of trypsinogen to a similar degree, but ribonuclease synthesis showed a significantly smaller increase of 53% over control. Insulin stimulated myosin and LDH synthesis by 169 and 184%, respectively. A differential pattern of protein synthesis was also observed when acini were treated with two other stimulators of protein synthesis, cholecystokinin and hemin. Both of these stimulators had a reduced effect on ribonuclease synthesis compared with amylase and trypsinogen synthesis but failed to increase myosin synthesis. When the RNAs extracted from control acini and acini treated with 100 nM insulin were translated in vitro, the proteins synthesized were quantitatively similar. This study therefore indicates that insulin has translational effects on acinar protein synthesis, and these effects are nonparallel for various specific acinar cell proteins.
Diabetes 1987 Sep
PMID:Insulin and other stimulants have nonparallel translational effects on protein synthesis. 330 74

It has been suggested that the gut hormone cholecystokinin (CCK), by modulating insulin output from pancreatic beta-cells, plays an important role in the enteroinsular axis. To investigate this hypothesis, eight rats were studied on two different occasions: after injection of L 364718, a specific antagonist of CCK binding to its membrane receptor, and after vehicle injection. In both studies a mixture of casein (11%) and glucose (9%) was infused through a chronic indwelling intraduodenal catheter to evoke CCK secretion. Plasma was analyzed for insulin, glucose, glucagon, and tyrosine many times during the procedure. Prior administration of the CCK antagonist significantly attenuated the increase in plasma insulin and glucagon after casein infusion. These results support the concept that cholecystokinin plays an important physiologic role in the in vivo regulation of postprandial plasma insulin and glucagon concentrations after protein ingestion.
Diabetes 1987 Oct
PMID:Physiological role of cholecystokinin in meal-induced insulin secretion in conscious rats. Studies with L 364718, a specific inhibitor of CCK-receptor binding. 330 89

Individuals with diabetes mellitus are reported to have a twofold to threefold increase in the incidence of cholesterol gallstones. A frequently cited but unproven pathophysiologic mechanism for this phenomenon is reduced gallbladder muscle function, which results in stasis and allows for cholesterol gallstone crystal formation and gallstone growth. To date, gallbladder motor function has not been investigated in a well-characterized diabetic population. Therefore, using radionuclide cholescintigraphy, gallbladder filling and subsequent emptying produced in response to an infusion of the octapeptide of cholecystokinin in 30 diabetic patients and 20 control individuals were studied. No difference in any parameter used to assess gallbladder filling was demonstrated in the diabetics when compared with controls. In contrast, gallbladder emptying induced with cholecystokinin-octapeptide (20 ng/kg body wt . h) was reduced in diabetics compared with controls (55% +/- 5% vs. 74% +/- 4%, p less than 0.01). The peak emptying rate in the diabetics was also decreased (5.0% +/- 0.5% per minute) compared with the controls (7.0% +/- 0.6% per minute, p less than 0.02). The observed decreased gallbladder emptying found in diabetics was not related to obesity, type of diabetes, diabetic control, or presence or absence of peripheral neuropathy. The most severe impairment of gallbladder emptying occurred, however, in diabetics with an associated autonomic neuropathy. This subgroup demonstrated a significant reduction in the percentage of gallbladder emptying (40% +/- 8% vs. 62% +/- 5%, p less than 0.04) and the peak ejection rate (3.5% +/- 0.5% per minute vs. 5.6% +/- 0.6%, p less than 0.02) compared with the diabetics without autonomic neuropathy.
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PMID:Impairment of gallbladder emptying in diabetes mellitus. 337 12

Calcitonin is known to inhibit secretion of gastrin and insulin in vivo. The objective of this study was to determine whether calcitonin can act directly on pancreatic islets in vitro to inhibit insulin release. Isolated islets were obtained from collagenase-treated rat pancreas, and three peptides (gastrin-releasing peptide, cholecystokinin-8, bombesin) and glucose were used to stimulate insulin release. All agents caused a significant increase in insulin secretion and calcitonin inhibited these responses, but had no consistent effect on basal release. This study provides evidence that calcitonin is an effective inhibitor of insulin secretion and acts directly on islet tissue.
Diabetes 1986 Jan
PMID:Calcitonin inhibition of insulin release from isolated rat pancreatic islets. 351 Jan 39

The internalization and intracellular distribution of 125I-insulin-like growth factor II (125I-IGF II) in mouse isolated pancreatic acini was studied by electron microscope autoradiography. 125I-IGF II was rapidly internalized; after 30 min over 70% of silver grains derived from the bound hormone were localized over the interior of the cells. The grain distribution from 125I-IGF II differed significantly from both a random grain distribution and that derived from bound 125I-insulin. The majority of intracellular 125I-IGF II grains were over the endoplasmic reticulum and Golgi; the Golgi showed the highest density of intracellular grains. Pretreatment of acini with 10 nM cholecystokinin octapeptide (CCK 8) reduced both the amount of acinar-associated IGF II and the density of intracellular 125I-IGF II grains. Moreover, CCK 8 altered the relative distribution of grains from 125I-IGF II between organelles. These studies indicate, therefore, that 125I-IGF II is internalized by pancreatic acini, and that this internalization is regulated by CCK 8.
Diabetes Res Clin Pract 1986 May
PMID:Autoradiographic analysis of 125I-insulin-like growth factor II internalization into pancreatic acini. 352 49

Preincubation of collagenase-isolated rat islets for 150 min with 100 U/ml purified human interleukin 1 (IL-1) altered their ability to secrete insulin. Whereas basal release rates with 4 mM glucose were comparable in control and IL-1-treated islets, both the first and second phases of release in response to 20 mM glucose were significantly reduced from IL-1-treated tissue. IL-1 pretreatment also impaired the secretory response to the combination of 100 nM cholecystokinin plus 7 mM glucose. However, the secretory response to 10 mM alpha-ketoisocaproate was comparable in control and IL-1-pretreated islets. Reducing the IL-1 exposure time to 60 min was accompanied by an augmented first phase of release to 20 mM glucose. Second phase secretion was diminished. The use of glucose measured after the perifusion was similar in control and IL-1-treated islets. Similar to other compounds that adversely impact on beta-cell viability, the inhibitory effect of IL-1 on release may presage a cytotoxic action of monokine.
Diabetes 1986 Oct
PMID:Interleukin 1 inhibits insulin secretion from isolated perifused rat islets. 353 Aug 42

Prior, short-term exposure of isolated perifused islets to cholecystokinin (CCK8S) sensitizes them to subsequent glucose stimulation. This sensitization effect develops quickly and persists long after the removal of CCK8S from the perifusion medium. Continued binding of CCK8S to its receptor on the beta-cell and the increase in glucose metabolism noted with glucose stimulation are essential for the full expression of this response. This sensitization process may play an integral role in the postulated incretin effect of the peptide.
Diabetes 1987 Jan
PMID:Prior cholecystokinin exposure sensitizes islets of Langerhans to glucose stimulation. 353 73

The effects of streptozotocin-induced diabetes on 125I-labeled epidermal growth factor (EGF) binding were studied in rat pancreatic acini. 125I-EGF binding was one-half maximal at 20 min, and maximal at 90 min. Saturation data revealed a decreased binding capacity in diabetic acini when compared with normal acini. Insulin, in vivo, normalized the decreased binding capacity. 125I-EGF internalization was also decreased in diabetic rat acini. Further, the inhibitory effect of cholecystokinin-octapeptide (CCK8) on cell-associated 125I-EGF radioactivity was significantly greater in diabetic than in normal rat acini. These findings suggest that insulin deficiency may lead to defective regulation of the exocrine pancreas by EGF.
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PMID:Epidermal growth factor binding is altered in pancreatic acini from diabetic rats. 609 11

The pancreatic islet hormone secretion is modulated by one or more gastrointestinal peptides ("gut-factor") secreted in response to various types of ingested nutrients. Among a number of postulated candidates for the putative "gut-factor", the gastric inhibitory polypeptide (GIP) has recently emerged as a most likely enteric signal of physiologic import, although its precise role in the pathophysiology of diabetes mellitus remains incompletely understood. During the past decade, an avalanche of knowledge has accumulated regarding a number of peptide agents common to the gastro-enteric-pancreatic system and the nervous system. Preliminary evidence indicates a potential role of several of these peptides in the pathophysiology of diabetes. For instance, cholecystokinin and human pancreatic polypeptide (hPP) may be importantly involved in the regulation of appetite and satiety control and the development of obesity whereas somatostatin, "endorphins", and neurotensin may directly or indirectly modulate islet hormone secretion. Finally the significance of the recently demonstrated presence of insulin and glucagon or glicentin-like peptides in the brain requires close scrutiny.
Diabetes Care
PMID:The role of gastrointestinal and neuronal peptides in the pathophysiology of diabetes mellitus. 612 74


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