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

The effect of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4), on arterial blood pressure and on the function of the isolated rat heart was studied in three groups of animals: normal (C group), rats with streptozotocin-induced diabetes of one month's duration (DM group) and with diabetes treated with insulin (DMI group). CCK-33 (5.0, 10.0 and 20.0 U/kg iv) raised dose-dependently systolic and diastolic arterial blood pressure but did not change the heart rate in the group of normal rats. CCK-33 administered in doses of 1.0, 2.0, 5.0 U/0.1 ml) increased the amplitude of the isolated heart contraction and reduced heart rate but had no effect on coronary outflow in this group. In the diabetic rats, CCK-33 in dose 20.0 U/kg iv reduced the arterial blood pressure and had no effect on heart rate in vivo. CCK-33 increased the cardiac contraction amplitude and lowered heart rate of the isolated heart from the diabetic rats. In the group of insulin-treated diabetic rats, CCK-33 did not change the blood pressure, increased the heart rate in vivo. This peptide increased the cardiac contraction amplitude, no lowering of the heart rate of the isolated heart was noted. CCK-8 and CCK-4 had no effect on arterial blood pressure and the function of the isolated heart in any of the groups of animals studied. The results indicate that shortening of CCK-33 to CCK-8 and CCK-4 eliminates the circulatory effect of this peptide and that in diabetes CCK-33 produces circulatory effects opposite to those observed in normal animals. Insulin partially normalizes the action of CCK-33 on the circulation in diabetes.
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PMID:Effects of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4), on the circulatory system of diabetic rats. 248 4

The endocrine, paracrine, and neurocrine influences of the non-glucose insulin secretion regulators on the pancreatic islets are analysed. Experiments on rats using the primary monolayer culture of isolated islet cells proved that insulin secretion is directly modulated by the growth hormone (GH), C-terminal tetrapeptide of cholecystokinin, thyroliberin, and met-enkephalin, and by certain blood plasma factors of diabetes I patients. In addition, GH is showed to stimulate the islet cell proliferation by intensifying 3H-thymidine incorporation into DNA synthesis. The blood plasma factors of IdDM patients influence the islets of Langerhans activity by either stimulating or depressing the secretory function of insulin producing cells. The aspects of functional organization of the islet cells and complex regulation of insulin secretion are discussed.
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PMID:[Mechanisms of the regulation of insulin secretion]. 250 84

We examined the effects of various stimuli on immunoreactive insulin (IRI) and glucagon (IRG) release from perfused pancreases isolated from control and streptozocin-induced diabetic (STZ-D) rats. Diabetes was induced by injecting 30 mg/kg STZ into rats fasted for 16-18 h 12-17 days before our experiments. Glucose (11.1 mM) caused a distinct biphasic pattern of IRI release from the control pancreas, whereas the first phase was marginal and the second phase was absent in the diabetic pancreas. Arginine (20 mM)-induced IRI release was similar in both groups, whereas IRG release was greater in the control rats than in the diabetic rats. Thus, this model of STZ-D simulates a certain class of non-insulin-dependent diabetes mellitus (NIDDM). In these diabetic animals, the cholecystokinin (CCK) analogue ceruletide (620 pM) caused a significantly greater increase in IRI release in the presence of 5.6 mM glucose than in the control rats, but ceruletide caused a similar IRG release in both groups. Because CCK and ceruletide stimulate phosphoinositide turnover in pancreatic islets, we examined the effects of carbachol and phorbol ester TPA on IRI release in the presence of 5.6 mM glucose. Carbachol (10 microM), which is thought to generate similar second messengers as ceruletide, induced greater IRI release in diabetic than in control rats. TPA (100 nM) caused a significantly greater increase in IRI release from the diabetic than the control pancreas. Our results demonstrate that the insulin-releasing mechanism involved in protein kinase C activation is enhanced in this model of NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Aug
PMID:Increased beta-cell secretory responsiveness to ceruletide and TPA in streptozocin-induced mildly diabetic rats. 252 62

The interaction of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4) with norepinephrine (NE) was studied in rats with streptozotocin (STZ)-induced diabetes. The rats, male Wistar, were divided into three groups: control, diabetic and insulin-treated diabetic. Twenty-eight days after STZ administration, the systolic and diastolic arterial blood pressure, heart rate and the function of the heart isolated by the Langendorff method were studied. NE caused a rise in systolic blood pressure in the control and insulin-treated diabetic rats, the opposite effect of NE was observed in diabetic rats. NE had no effect on heart rate in any of the groups studied. CCK-33 potentiated the hypertensive effect of NE in the control rats reduced the hypertensive effect of this amine in diabetic rats treated with insulin and its hypotensive effect in the diabetic rats. CCK-8 did not change the NE effect on arterial blood pressure in the control and insulin-treated diabetic rats but did reduce the hypotension caused by NE in diabetic rats. CCK-4 did not change the effects of NE in any of the groups. NE induced an increase in cardiac contraction amplitude in all rats but its positive inotropic action was found to be the weakest in the diabetic rats. Administration of CCK-33 did not change the positive inotropic effect of NE in any of the groups but did, however, weaken its influence on heart rate in diabetic rats and insulin-treated diabetic rats. CCK-8 reduced the positive inotropic action of NE but did not affect its chronotropic effect. CCK-4 had no effect on the action of NE in any of the groups. Diabetes can change the response of alpha-adrenergic system to CCK-33 and NE. Insulin partially normalized the circulatory system response in the diabetic rats.
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PMID:The interaction of cholecystokinin and its fragments with norepinephrine in the circulatory system of diabetic rats. 257 26

Morbid obesity is a major health problem in this country and throughout the world. In addition to its social stigma (in the western world), obesity exacerbates several disease states such as diabetes, hypertension, cardiac disease and restrictive lung disease. When effective medical treatment of obesity becomes available, it will depend in part upon understanding the physiologic factors that control satiety. This review summarizes the information available on brain and gut control mechanisms of satiety. Brain nuclei located in the lateral hypothalamus, ventromedial hypothalamus, and other paraventricular areas are the sites of action for potent neuropeptides, such as cholecystokinin (CCK) and neuropeptide Y, that appear to regulate feeding. Exogenous CCK has been used clinically to decrease meal size in obese patients. The sites of the satiety cascade that are most often manipulated are the gastric and intestinal phases. Physiologic gastric distension is a potent inhibitor of feeding, whereas the intermeal interval may be regulated by intestinal signals released by food in the gut. Jejunal-ileal bypass has fallen from favor and has been replaced by gastric restrictive procedures that create a small proximal gastric pouch that empties into the small bowel (gastric bypass) or the distal stomach (gastroplasty). These operations rely partially on their ability to produce gastric distension in the proximal gastric pouch at an early stage during a meal. Thus, failure results if the pouch compensates by distending or if the stoma widens with subsequent loss of slow emptying. Improved medical and surgical treatment will be designed to intervene at specific sites of the satiety cascade as knowledge of the physiologic control mechanisms of satiety increases.
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PMID:Physiologic approaches to the control of obesity. 229 39

Our aim was to isolate and determine the contribution of partial pancreatectomy, systemic delivery of pancreatic hormones, and duct obliteration to glucose regulation after segmental pancreas transplantation in dogs. Fasting, postprandial, and intravenous glucose-stimulated glucose, insulin, glucagon, pancreatic polypeptide (PP), and cholecystokinin (CCK) and intravenous bombesin-stimulated PP levels were studied in beagles at three successive intervals in a crossover design. The first was 6 wk after partial (approximately 70%) pancreatectomy with intact regular enteric exocrine drainage from the duodenal pancreatic remnant, the next was 2 wk after venous transposition with systemic delivery of pancreatic hormones, and the third was 6 wk after in situ duct obliteration of the remnant. With partial pancreatectomy, K values were modestly diminished (30%), and a concomitant reduction of second-phase intravenous glucose-stimulated insulin release was observed. Other parameters were not significantly affected. Venous transposition doubled peripheral plasma levels of insulin under all conditions. Fasting glucose, PP, and CCK levels decreased slightly. Other parameters were not affected. Duct obliteration of the systemic draining pancreatic remnants seriously impaired glucose sensitivity, resulting in a 50% reduction of K values and fasting and sustained postprandial hyperglycemia (approximately 8 mM) and a 70-50% reduction (acute and overall responses, respectively) of intravenous glucose-stimulated insulin. Fasting hormone and postprandial insulin, glucagon, and CCK levels were not affected. The postprandial PP response was severely reduced, and bombesin-stimulated PP release was abolished by duct obliteration. We conclude that histological changes associated with duct obliteration are the major determinants of glucose regulation in segmental pancreas transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Sep
PMID:Contribution of partial pancreatectomy, systemic hormone delivery, and duct obliteration to glucose regulation in canine pancreas. Importance in pancreas transplantation. 267 Jun 40

Cholecystokinin (CCK) is a well-characterized gastrointestinal hormone which is released into the general circulation after meals. Targets for CCK include not only the gallbladder and the exocrine pancreas but also the endocrine pancreas. In this paper, we review the role of CCK from the perspective of the entero-insular axis, where CCK seems to function as one component of incretin and can raise insulin release synergistically with other incretin components. CCK also increases the sensitivity of B cells to subsequent glucose stimulation. At present, the role of CCK as incretin in disease states is uncertain. The pathophysiological role of CCK is likely to be revealed using CCK-specific radioimmunoassay and bioassay techniques and CCK receptor antagonists.
Diabetes Res Clin Pract 1989
PMID:Cholecystokinin in the entero-insular axis. 268 Mar 70

Development of a robust insulin secretory response to glucose occurs during the early neonatal period. To determine if neuroendocrine agents play a role during this time, we studied the effects of selected peptides and neurotransmitters on insulin release and polyphosphoinositide metabolism in islets isolated from 1- and 3-day neonatal rats. Vasoactive intestinal peptide had no effect on glucose-stimulated release in either islet population. In contrast, sulfated cholecystokinin octapeptide (CCK-8) significantly enhanced glucose-induced insulin release in both islet groups. One-day islets were stimulated only by a concentration of 300 nM, whereas 3-day islets were responsive at 3 nM. Similar to CCK-8, there were clear differences in responses to carbachol between 1- and 3-day islets. One-day islets required a concentration of 200 microM for insulin release to be significantly greater than with glucose alone; 3-day islet insulin release was significant at 2 microM carbachol. Both agonists stimulated inositol phosphate accumulation in 3-day islets, but only CCK-8 caused a significant increase over glucose-induced levels in 1-day islets. These results indicate that islet responsiveness to CCK-8 and carbachol develops in parallel during the early neonatal period. This development may be linked to the maturation of a critical step of stimulus-secretion coupling through which these agents act.
Diabetes 1989 Nov
PMID:Age-dependent stimulation of neonatal insulin release and inositol phosphate accumulation by CCK-8 and carbachol. 269 70

Prior exposure of isolated perifused rat islets to the sulfated gut hormone cholecystokinin-8 (CCK-8S) dramatically increased their insulin secretory response to 7.5 mM glucose, 10 mM arginine, and 10 mM alpha-ketoisocaproate. In the case of glucose, the heightened secretory response was still apparent 60-80 min after CCK-8S removal from the perifusion medium. Prior exposure of perifused islets to arginine (10 mM), tolbutamide (25 microM), or forskolin (1.0 microM) did not sensitize them to 7.5 mM glucose. CCK-8S exposure increased 3H efflux from islets prelabeled with [3H]inositol, and the increase in 3H efflux was sustained after CCK-8S removal from the perifusion medium. The duration of this increase in 3H efflux paralleled the temporal characteristics of this sensitization process and was significantly attenuated by 25 microM asperlicin, a competitive antagonist of CCK binding to its membrane receptor. Arginine, tolbutamide, or forskolin treatment of islets did not increase 3H efflux from [3H]inositol-prelabeled islets. The results suggest that the turnover of membrane phosphoinositides induced by CCK-8S is largely responsible for this heightened state of secretory responsiveness to various stimulants. Second-messenger molecules generated during phosphoinositide turnover may be responsible for the phenomenon of sensitization displayed by islet tissue to CCK-8S addition.
Diabetes 1987 Dec
PMID:Cholecystokinin-induced alterations in beta-cell sensitivity. Duration, specificity, and involvement of phosphoinositide metabolism. 282 61

The influence of cyclic AMP (cAMP) and extracellular calcium on phosphoinositide (PI) hydrolysis in isolated islets was assessed and related to insulin output. Three stimulants were chosen to activate the beta-cell: sulfated cholecystokinin (CCK-8S, 200 nM), high-level glucose (20 mM), and the sulfonylurea tolbutamide (200 microM). The insulin secretory response to all three agonists was amplified by forskolin (which increases cAMP levels) and reduced by nitrendipine (which decreases calcium influx). All three stimulants increased the hydrolysis of inositol-containing phospholipids, an event monitored by an increase in [3H]inositol efflux from [3H]inositol-prelabeled islets and by the accumulation of labeled inositol phosphates. Forskolin, despite its positive impact on insulin secretion, reduced [3H]inositol efflux and inositol phosphate accumulation in response to all agonists. A similar inhibitory effect on these parameters was noted with nitrendipine; however, nitrendipine abolished secretion in response to all agonists. These findings support the following conclusions: 1) an increase in cellular cAMP levels reduces the quantitative impact of various agonists on these indices of PI hydrolysis; 2) despite this inhibitory effect, cAMP amplifies the insulin secretory response to these agonists; and 3) extracellular calcium is a crucial determinant of both PI hydrolysis and the ensuing insulin secretory response.
Diabetes 1988 Nov
PMID:Influence of cAMP and calcium on [3H]inositol efflux, inositol phosphate accumulation, and insulin release from isolated rat islets. 284 90


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