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Biomedical subjects

S Efendic

Publications and source records attributed to S Efendic.

At least 73 records · Page 4Linked to original sources
PubMed1998

Inhibitory effect of glucagon-like peptide-1 on small bowel motility. Fasting but not fed motility inhibited via nitric oxide independently of insulin and somatostatin.

Effects of glucagon-like peptide-1 (GLP-1)(7-36)amide on fasted and fed motility in the rat small intestine were investigated in relation to its dependence on nitric oxide (NO), insulin, and somatostatin. Small bowel electromyography was performed using bipolar electrodes implanted 15, 25, and 35 cm distal to pylorus, and transit was studied with a radioactive marker. In the fasted state, GLP-1 (5-20 pmol kg-1min-1), reaching physiological plasma levels, prolonged the migrating myoelectric complex (MMC) cycle length along with slowed transit. This effect was antagonized by exendin(9-39)amide. The NO synthase inhibitor Nomega-nitro- L-arginine (L-NNA) also blocked the response to GLP-1, whereas L-arginine restored the response. Insulin (80-200 pmol kg-1min-1) induced irregular spiking, whereas somatostatin (100-500 pmol kg-1min-1) increased the MMC cycle length, independently of NO. In the fed state, GLP-1 (20-40 pmol kg-1min-1) reduced motility, an inhibition unaffected by L-NNA, whereas motility was stimulated by exendin(9-39)amide. Infusion of GLP-1 (20-100 pmol kg-1min-1) did not affect plasma insulin, but somatostatin was increased. In conclusion, GLP-1 seems to inhibit small bowel motility directly via the GLP-1 receptor. Inhibition of fasting motility is dependent of NO and not mediated via insulin or somatostatin, whereas inhibition of fed motility is independent of NO.

Animals↗
PubMed1998

Effects of 3-mercaptopicolinic acid and a derivative of chlorogenic acid (S-3483) on hepatic and islet glucose-6-phosphatase activity.

Glucose-6-phosphatase activity was measured in hepatic microsomes and in pancreatic islets from ob/ob mice. In hepatic microsomes vanadate, phlorizin, 3-mercaptopicolinic acid and a derivative of chlorogenic acid (S-3483) inhibited the translocase activity of the enzyme, vanadate in addition inhibited hydrolase activity. In islets, vanadate inhibited both components of the enzyme, phlorizin inhibited only hydrolase activity while 3-mercaptopicolinic acid and compound S-3483 were without effect. Similarly, when islets were incubated with 3H2O and unlabeled glucose, the incorporation of 3H into medium glucose was inhibited by vanadate and phlorizin, but not by 3-mercaptopicolinic acid and S-3483. These findings suggest that, as with glucokinase, different isoenzymes of glucose-6-phosphatase are present in islets and liver.

Animals↗
PubMed1998

Increased glucocorticoid sensitivity in islet beta-cells: effects on glucose 6-phosphatase, glucose cycling and insulin release.

Glucose-6-phosphatase (G6Pase) activity and the rate of glucose cycling are increased in islets from animal models of Type II (non-insulin-dependent) diabetes mellitus. Glucocorticoid treatment further stimulates these processes and inhibits glucose-induced insulin release. To determine whether these effects result from a direct action of glucocorticoids on the beta-cells, we used isolated islets. The islets were from transgenic mice overexpressing the glucocorticoid receptor in their beta-cells to increase the cells' sensitivity to glucocorticoid. Islets from transgenic and non-transgenic control mice utilized and oxidized the same amount of glucose. In contrast, islet G6Pase activity was 70 % higher, glucose cycling was increased threefold and insulin release was 30 % lower in islets from transgenic mice. Hepatic G6Pase activity was the same in transgenic and control mice. Dexamethasone administration increased G6Pase activity and glucose cycling and decreased insulin release in both transgenic and control mouse islets. We conclude that glucocorticoids stimulate islet G6Pase activity and glucose cycling by acting directly on the beta-cell. That activity may be linked to the inhibition of insulin release.

Animals↗
PubMed1998

Preserved initiatory and potentiatory effect of alpha-ketoisocaproate on insulin release in islets of glucose intolerant rats.

Insulin responses to glucose and non-glucose secretagogues were studied in short-term cultured pancreatic islets and perfused pancreata of the glucose intolerant F1 hybrid rats of spontaneously diabetic Goto-Kakizaki and control Wistar rats. After culture at 5.5 mmol/l glucose, hybrid islet responses to 11.1, 16.7 and 27.0 mmol/l glucose were between 60 and 40% of control islet responses. A combination of 1 mmol/l isobutylmethylxanthine and 16.7 mmol/l glucose induced a pronounced insulin release, which was of similar magnitude in hybrid and control rat islets. This response was not further augmented by addition of glibenclamide and arginine. The slope of potentiation of arginine (10 mmol/l)-stimulated insulin secretion by glucose (5.5-16.7 mmol/l) was greatly impaired in hybrid islets. In contrast to glucose, alpha-ketoisocaproate (KIC), which is metabolized in Krebs cycle, dose-dependently stimulated insulin secretion to similar levels in hybrid and control islets, cultured at 5.5 mmol/l glucose. Also in hybrid islets depolarized by potassium chloride (30 mmol/l) and with adenosine triphosphate-sensitive K+-channels kept open by diazoxide, insulin responses to glucose were greatly impaired but intact to KIC. Furthermore, KIC potentiated normally the insulin response to arginine in hybrid islets. In the isolated perfused pancreas, KIC induced similar insulin responses in hybrid rats and control rats. The potentiating effect by 5.5 mmol/l glucose on the KIC-stimulated insulin responses was, however, greatly reduced in isolated islets and absent in the perfused pancreata of hybrid rats. Taken together, these findings suggest an intact capacity for insulin release, although the initiating and potentiating effect by glucose on insulin release are defective in the Goto-Kakizaki-hybrid rats. An abnormal beta-cell glucose metabolism proximal to the Krebs cycle is likely to account for the impairment of insulin release.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Glucose-6-phosphatase activity in the hypothalamus of the ob/ob mouse.

The hypothalamus and cortex from ob/ob mice and their lean littermates were sonicated and then incubated with glucose-6-phosphate (glucose-6-P) and glycerol phosphate (glycerol-P). The difference between the rates of hydrolysis of glucose-6-P and glycerol-P was taken as the measure of glucose-6-phosphatase activity. The activity was much higher in the hypothalamus from ob/ob mice versus their lean littermates. Activity was undetected in the cortex. These findings raise the possibility that a defect in the regulation of glucose-6-phosphatase activity in a portion of the hypothalamus may relate to the mechanism underlying obesity in the ob/ob mouse. However, obese gene product administration to ob/ob mice, while reducing the body weight, did not alter the glucose-6-phosphatase activity.

Animals↗
PubMed1998

Preoperative oral carbohydrate administration reduces postoperative insulin resistance.

UNLABELLED: Infusions of carbohydrates before surgery reduce postoperative insulin resistance. We in-vestigated the effects of a carbohydrate drink, given shortly before surgery, on postoperative metabolism. METHOD: Insulin sensitivity, glucose turnover ([6,6, 2H2]-D-glucose) and substrate utilization were measured using hyperinsulinemic normoglycemic clamps and indirect calorimetry in two matched groups of patients before and after elective colorectal surgery. The drink group (n = 7) received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation (100 g carbohydrates), as well as another 400 ml (50 g carbohydrates) 2 h before the initiation of anesthesia. The fasted group (n = 7) was operated after an overnight fast. RESULTS: After surgery, energy expenditure increased in both groups. Endogenous glucose production was higher after surgery and the difference was significant during low insulin infusion rates in both groups (P < 0.05). The supressibility of endogenous glucose production by the two step insulin infusion was similar pre-and postoperatively in both groups. At the high insulin infusion rate postoperatively, whole body glucose disposal was more reduced in the fasted group (-49 +/- 6% vs -26 +/- 8%, P < 0.05 vs drink). Furthermore, during high insulin infusion rates, glucose oxidation decreased postoperatively only in the fasted group (P < 0. 05) and postoperative levels of fat oxidation were greater in the fasted group (P < 0.05 vs drink). Only minor postoperative changes in cortisol and glucagon were found and no differences were found between the treatment groups. CONCLUSIONS: Patients given a carbohydrate drink shortly before elective colorectal surgery displayed less reduced insulin sensitivity after surgery as compared to patients who were operated after an overnight fast.

Adolescent↗
PubMed1998

Glucagon-like peptide-1 retards gastric emptying and small bowel transit in the rat: effect mediated through central or enteric nervous mechanisms.

This study investigated effects of glucagon-like peptide-1(7-36)amide (GLP-1) on gastric emptying, small intestinal transit, and contractility of smooth muscle strips in rats. GLP-1 at doses of 10 and 20 pmol/kg/min administered intravenously dose-dependently retarded transit of the small intestine (P < 0.001), while only the higher dose of 20 pmol/kg/min retarded gastric emptying (P < 0.01). GLP-1 at concentrations up to 10(-4) M did not affect the basal tone or contractility of the gastrointestinal muscle strips that were stimulated with electric field stimulation or acetylcholine. Our results demonstrate that small intestinal transit seems more sensitive than gastric emptying to inhibition by GLP-1 at physiologic levels in plasma. Furthermore, this inhibition appears to be mediated through central mechanisms rather than through peripheral actions. Thus, GLP-1 is suggested to inhibit gastric emptying and small intestinal transit through an indirect effect via central or enteric nervous mechanisms.

Acetylcholine↗
PubMed1998

Progression of coronary artery disease in young male post-infarction patients is linked to disturbances of carbohydrate and lipoprotein metabolism and to impaired fibrinolytic function.

AIMS: To assess determinants of coronary artery disease progression in men with previous myocardial infarction. METHODS AND RESULTS: A total of 102 unselected non-diabetic Swedish men (age 40.4 +/- 3.6, range 23-44 years) entered the study 3-6 months after a first myocardial infarction. The programme included metabolic and haemostatic investigations and routine coronary angiography at baseline, followed by re-angiography 5 years later. Of the original cohort, 76 patients underwent a second angiogram. Separate semiquantitative scoring systems were used for diffuse coronary atherosclerosis and distinct stenoses in 15 proximal coronary segments. Smoking, global severity of coronary atherosclerosis and presence of multi-vessel disease at baseline (P < 0.001) characterized patients with severe progression of both diffuse and focal lesions. Higher plasma levels of low density lipoprotein cholesterol (P < 0.01) and low density lipoprotein triglycerides (P < 0.05), a lower plasma high density lipoprotein2 cholesterol level (P < 0.05) and higher plasma plasminogen activator inhibitor-1 activity (P < 0.05), together with a high baseline stenosis score (P < 0.001) characterized patients with severe progression of coronary atherosclerosis. On the other hand, more pronounced fasting and post-prandial glycaemia (P < 0.05), together with higher plasma plasminogen activator inhibitor-1 activity (P < 0.01) characterized severe progressors with respect to coronary stenosis. Multivariate analysis identified the presence of multi-vessel disease as an independent predictor of progression of both coronary atherosclerosis (P = 0.008) and stenoses (P = 0.007), whereas a high low density lipoprotein triglyceride level (P < 0.01) was independently related to progression of coronary atherosclerosis and a high fasting glucose level (P = 0.02) to progression of coronary stenoses. CONCLUSION: Disturbances in carbohydrate and lipoprotein metabolism and impaired fibrinolytic function are associated with progression of coronary artery disease in young male post-infarction patients.

Adult↗
PubMed1998

Perioperative insulin and glucose infusion maintains normal insulin sensitivity after surgery.

Elective surgery was performed after overnight fasting, a routine that may affect the metabolic response to surgery. We investigated the effects of insulin and glucose infusions before and during surgery on postoperative substrate utilization and insulin sensitivity. Seven patients were given insulin and glucose infusions 3 h before and during surgery (insulin group), and a control group of six patients underwent surgery after fasting overnight. Insulin sensitivity and glucose kinetics (D-[6,6-2H2]glucose) were measured before and immediately after surgery using a hyperinsulinemic, normoglycemic clamp. Glucose infusion rates and whole body glucose disposal decreased after surgery in the control group (-40 and -29%, respectively), whereas no significant change was found in the insulin group (+16 and +25%). Endogenous glucose production remained unchanged in both groups. Postoperative changes in cortisol, glucagon, fat oxidation, and free fatty acids were attenuated in the insulin group (vs. control). We conclude that perioperative insulin and glucose infusions minimize the endocrine stress response and normalize postoperative insulin sensitivity and substrate utilization.

Arthroplasty, Replacement, Hip↗
PubMed1998

Glucose metabolism in Goto-Kakizaki rat islets.

Islets from Goto-Kakizaki (GK) rats from our colony, despite marked impairment of glucose-induced insulin release, used glucose and produced CO2 at a rate 3 times that of islets from control Wistar rats. Almost all glucose used was accounted for in CO2 and lactate production. The percentages of glucose carbon used collected in CO2 and lactate were similar for control and GK islets. GK islets also oxidized 40% more acetate and leucine to CO2 than did control islets. The fraction of carbon leaving the Krebs cycle relative to CO2 production was the same in GK and control islets. The capacities of mitochondria from GK islets to generate ATP from glutamate and malate were similar and that to generate ATP from succinate and rotenone was somewhat less from GK islets. The reason for the enhanced utilization of substrates by islets of the GK rat is not apparent. In conclusion, there is no decrease in islet glucose utilization, glucose oxidation, Krebs cycle function, or the electron transport system evident from these measurements to explain the impaired insulin release in islets from GK rats.

Acetates↗
PubMed1997

Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats.

A bioactive macrophage factor, the polypeptide daintain/allograft inflammatory factor 1 (AIF1), has been isolated from porcine intestine. It was discovered when searching for intestinal peptides with effects on insulin release, and its purification was monitored by the influence of the peptide fractions on pancreatic glucose-induced insulin secretion. Daintain/AIF1 is a 146-aa residue polypeptide with a mass of 16,603 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern -KR-KK-GKR- has a motif typical of peptide hormone precursors, i.e., dibasic sites for potential activation cleavages and at the sequentially last such site, the structure GKR. The latter is a signal for C-terminal amide formation in the processing of peptide hormones. Daintain/AIF1 is immunohistochemically localized to microglial cells in the central nervous system and to dendritic cells and macrophages in several organs. A particularly dense accumulation of daintain/AIF1-immunoreactive macrophages was observed in the insulitis affecting the pancreatic islets of prediabetic BB rats. When injected intravenously in mice, daintain/AIF1 at 75 pmol/kg inhibited glucose (1 g/kg)-stimulated insulin secretion, with a concomitant impairment of the glucose elimination, whereas at higher doses (7.5 and 75 nmol/kg), daintain/AIF1 potentiated glucose-stimulated insulin secretion and enhanced the glucose elimination. Its dual influence on insulin secretion in vivo at different peptide concentrations, and the abundance of macrophages expressing daintain/AIF1 in the pancreatic islets of prediabetic rats, suggest that daintain/AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus.

Amino Acid Sequence↗
PubMed1997

Characterization of dopuin, a polypeptide with special residue distributions.

A 62-residue polypeptide, dopuin, has been isolated from pig small intestine. It is distinguished by an N-terminal part with a high content of proline (7 in a 26-residue segment), a C-terminal part with a high proportion of histidine (3 in a 9-residue segment), and six half-cystine residues in three intrachain disulphide bridges (connecting positions 22-25, 23-54 and 35-44). The Cys and Pro distributions suggest a tight and special conformation. In contrast to PEC-60 and somatostatin, it has no established inhibitory effect on insulin secretion. At 10 nM concentration, a weak inhibitory tendency is less than half of that of the other two peptides. Like gastrointestinal trefoil peptides, dopuin has three disulphide bridges, Ala-Pro segments, and many charged residues, but they are differently distributed and dopuin belongs to a separate, apparently novel family. However, dopuin is similar to a peptide corresponding to an expressed-sequence-tag cDNA of human fetal liver and spleen, establishing the nature of the mature form of the product of this cDNA, and showing a general tissue, age, and species distribution of this peptide. A truncated form of vimentin, composed of its C-terminal 37 residues, vimentin-C37, was also purified and structurally characterized. These two peptides increase the complexity of known intestinal polypeptides and at least dopuin has properties compatible with specific biofunctions.

Amino Acid Sequence↗
PubMed1997

Pancreatic beta cells are important targets for the diabetogenic effects of glucocorticoids.

Abnormalities contributing to the pathogenesis of non-insulin-dependent diabetes mellitus include impaired beta cell function, peripheral insulin resistance, and increased hepatic glucose production. Glucocorticoids are diabetogenic hormones because they decrease glucose uptake and increase hepatic glucose production. In addition, they may directly inhibit insulin release. To evaluate that possible role of glucocorticoids in beta cell function independent of their other effects, transgenic mice with an increased glucocorticoid sensitivity restricted to their beta cells were generated by overexpressing the glucocorticoid receptor (GR) under the control of the insulin promoter. Intravenous glucose tolerance tests showed that the GR transgenic mice had normal fasting and postabsorptive blood glucose levels but exhibited a reduced glucose tolerance compared with their control littermates. Measurement of plasma insulin levels 5 min after intravenous glucose load demonstrated a dramatic decrease in acute insulin response in the GR transgenic mice. These results show that glucocorticoids directly inhibit insulin release in vivo and identify the pancreatic beta cell as an important target for the diabetogenic action of glucocorticoids.

Animals↗
PubMed1997

Full-length and N-terminally truncated chicken intestinal diazepam-binding inhibitor. Purification, structural characterization and influence on insulin release.

Two forms of diazepam-binding inhibitor (DBI) have been purified from chicken intestine and identified as the intact avian polypeptide (residues 1-86) and a truncated variant (residues 35-86). At 10 nM concentration, both the intact and the truncated peptide suppress in vitro-monitored glucose-induced insulin release by 50 (p < 0.02) and 64% (p < 0.01) respectively. The truncation starts at a segment. -Thr-Val-Gly-Asp-, that is strictly conserved between characterized DBI species, indicating special restrictions on the structure. However, overall DBI conservation appears to be complex. A number of differently bioactive fragments with separate processings and tissue distributions have been observed, suggesting multiple functions of DBI and its sub-segments.

Amino Acid Sequence↗
PubMed1997

Truncated and full-length glucagon-like peptide-1 (GLP-1) differentially stimulate intestinal somatostatin release.

Glucagon-like peptide-1(7-36NH2) is a potent stimulator of insulin secretion, as well as of somatostatin-14 (SS-14) release from the pancreatic and gastric D-cells. To investigate the possible effects of this peptide on release of intestinal somatostatin (SS-28 and SS-14, rat intestinal cultures were treated with 10(-12)-10(-6) M GLP-1(7-36NH2), as well as with the structurally related peptides, GLP-1(1-36NH2) and GLP-2. Both forms of GLP-1 stimulated does-dependent increases in intestinal somatostatin; secretion reached 643 +/- 126% of controls (p < 0.001) after treatment with 10(-6) M GLP-1(7-36NH2), and 398 +/-76% of controls (p < 0.001) after 10(-6) M GLP-1(1-36NH2). Thus, GLP-1(7-36NH2) was more effective than GLP-1(1-36NH2) in stimulating secretion of intestinal somatostatin-like immunoreactivity (SLI) (p < 0.05). GLP-2 did not affect intestinal somatostatin release. Gel permeation analysis demonstrated that 10(-6) M GLP-1(7-36NH2) stimulated SS-28 by 2.9 +/- 0.4-fold and SS-14 by 9.1 +/- 3.7-fold, whereas GLP-1(1-36NH2) exerted equivalent effects (2.8 +/- 0.9-fold) on both forms of somatostatin. These findings define a novel biological role for GLP-1(7-36NH2) in the regulation of intestinal somatostatin secretion, and demonstrate that GLP-1(1-36NH2) exerts unique biological activities in this system.

Animals↗
PubMed1997

Gastric inhibitory polypeptide and splanchnic blood perfusion: augmentation of the islet blood flow increase in hyperglycemic rats.

The aim of the study was to investigate how the incretin candidate hormone gastric inhibitory polypeptide (GIP) affects splanchnic blood flow, especially pancreatic islet blood flow. For this purpose, male Sprague-Dawley rats were injected intravenously with either saline or GIP (5 or 15 micrograms/kg body weight) 10 min before blood flow measurements by a microsphere technique. Furthermore, 3 min before the blood flow measurements, 1 ml of either saline or 30% D-glucose was given intravenously. All glucose-injected animals were markedly hyperglycemic (> 20 mmol/liter) at the time of the blood flow measurements. Both doses of GIP potentiated basal and glucose-stimulated insulin release. In the normoglycemic rats, the lowest dose of GIP did not affect the blood perfusion to any of the investigated organs. The highest dose of GIP decreased whole pancreatic and duodenal blood flow, whereas islet blood flow was unaffected. As a result, fractional islet blood flow was increased. In the hyperglycemic rats, where the islet blood flow was increased compared with control animals, both doses of GIP further enhanced islet blood flow. No effect on pancreatic, fractional islet, or duodenal blood flow was seen after GIP administration to hyperglycemic animals. It is concluded that administration of GIP can further augment the glucose-induced stimulation of islet blood flow. This may contribute to facilitating release of insulin from the islets.

Animals↗
PubMed1997

Site of insulin resistance after surgery: the contribution of hypocaloric nutrition and bed rest.

1. Insulin resistance after surgery has been shown to be related to several important derangements in protein and fat metabolism. However, mechanisms of impaired glucose tolerance after surgery remain ill-defined. 2. Insulin sensitivity and glucose kinetics (6,6(2)H2-glucose) were studied in seven patients before and after elective surgery (surgery group), by two step-hyperinsulinaemic (0.3 and 0.8 munits kg-1 min-1), normoglycaemic (4.5 mmol/l) clamps. Six healthy subjects were studied, using the same protocol, before and after a similar period of bed rest and hypocaloric nutrition (fast/bed rest group) to delineate the effects of surgery per se. 3. Basal endogenous glucose production and whole-body glucose disposal was higher after surgery (P < 0.001), whereas no change was found after fast/bed rest. During glucose clamps, the glucose infusion rates required to maintain normoglycaemia and whole-body glucose disposal decreased (P < 0.001) after surgery, while endogenous glucose production increased (P < 0.001). In the control subjects, levels of endogenous glucose production remained unchanged after fast/bed rest. In contrast, glucose infusion rates and whole-body glucose disposal during glucose clamps also decreased after fast/bed rest (P < 0.01). However, the relative decrease in both these parameters was greater after surgery compared with after fast/bed rest (P < 0.01). 4. After surgery, energy expenditure and fat oxidation increased (P < 0.001), whereas glucose oxidation decreased (P < 0.05). No significant change was found in glucose utilization postoperatively. After fast/bed rest, no change was found in energy expenditure. However, fat oxidation increased (P < 0.01), whereas glucose oxidation and glucose utilization decreased (P < 0.05). 5. In conclusion, impaired glucose tolerance develops after surgery as a result of decreased insulin-stimulated whole-body glucose disposal as well as increased endogenous glucose release. Despite the increase in endogenous glucose production, the reduction in endogenous glucose production with each elevation of insulin was unaffected by surgery. Perioperative bed rest and/or hypocaloric nutrition contribute to the decrease in insulin-stimulated whole-body glucose disposal in the post-operative state, whereas these factors have no effects on endogenous glucose production.

Adult↗