| 11. |
- Qader, Saleem, et al.
(författare)
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Long-term infusion of nutrients (total parenteral nutrition) suppresses circulating ghrelin in food-deprived rats.
- 2005
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 131:Aug 12, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ghrelin derives from endocrine cells (A-like cells) in the stomach (mainly the oxyntic mucosa). Its concentration in the circulation increases during fasting and decreases upon re-feeding. This has fostered the notion that the absence of food in the upper gastrointestinal (GI) tract stimulates the secretion of ghrelin. The purpose of the present study was to determine the concentration of ghrelin in serum and oxyntic mucosa after replacing food with intravenous (iv) infusion of nutrients for 8 days using the technique known as total parenteral nutrition (TPN). Materials and methods: Male Sprague-Dawley rats (200-250 g) were given nutrients (lipids, glucose, amino acids, minerals and vitamins) by iv infusion for 8 days during which time they were deprived of food and water; another group was deprived of food for 24-48 h (fasted controls), while fed controls had free access to food and water. Serum ghrelin, gastrin and pancreastatin concentrations were measured together with the ghrelin content of the oxyntic mucosa. Plasma insulin and glucose as well as serum lipid concentrations were also determined. Results: Fasted rats had higher serum ghrelin than TPN rats and fed controls. The oxyntic mucosal ghrelin concentration (and content) was lower in TPN rats than in fasted rats or fed controls. The serum gastrin and pancreastatin concentrations were lower in TPN rats and fasted rats than in fed controls. The plasma insulin concentration was 87 pmol/l +/- 8 (SEM) in TPN rats compared to 101 16 pmol/l in fed controls; it was 26 14 pmol/l in fasted rats. The basal plasma glucose level was 11 +/- 0.6 mmol/l in TPN rats and 12 +/- 0.8 mmol/l in fed controls; it was 7 +/- 0.3 mmol/l in fasted rats. In TPN rats, the serum concentrations of free fatty acids, triglycerides and cholesterol were increased by 100%, 50% and 25%, respectively, compared to fed controls. Fasted rats had higher circulating concentrations of free fatty acids (20%) and lower concentrations of triglycerides (- 40%) than fed controls; fasted rats did not differ from fed controls with respect to serum cholesterol. Conclusion: The circulating ghrelin concentration is high in situations of nutritional deficiency (starvation) and low in situations of nutritional plenty (free access to food or TPN). The actual presence or absence of food in the GI tract seems irrelevant. Circulating insulin and glucose concentrations did not differ much between TPN rats and fed controls, serum lipids, however, were elevated in the TPN rats. We suggest that elevated blood lipid levels contribute to the suppression of circulating ghrelin in rats subjected to TPN for 8 days.
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| 12. |
- Qader, Saleem
(författare)
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Nitric Oxide Synthase in Pancreatic Islets During Trauma and Parenteral Feeding
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The influence of trauma (acute pancreatitis) or total parenteral nutrition (TPN) on pancreatic islet hormone secretion in relation to islet expression of inducible nitric oxide synthase (iNOS) was investigated. Acute pancreatitis resulted in an impaired glucose-stimulated insulin secretion (GSIS) which was found to be parallelled by a marked expression of iNOS and an exaggerated NO production in the pancreatic islets. A characteristic feature of long term TPN-treatment is hyperlipidemia and euglycaemia, since the major component of TPN solution is intralipid (IL). TPN treatment impairs GSIS at least in part through a reduced cyclic AMP production in parallel with an exclusive expression of iNOS, which was reflected in an increased NO production accompanied by enhanced cyclic GMP formation by islets. Agents stimulating cyclic AMP/Protein kinase A (PKA) i.e. PACAP27 and PACAP38 were capable of not only inhibiting neuronal constitutive NOS (ncNOS) but also counteracting the expression of iNOS induced by intralipid infusion. The suppressed NO production in the presence of PACAPs was reflected in a suppressed cyclic GMP and a marked increase in cyclic AMP production by pancreatic islets. A short-term study revealed that a "hyperglycaemic or hyperlipidemic period" as short as 24 hours stimulated the expression and activity of iNOS in the islets. Finally the effect of ghrelin (gastric hormone) on islet hormone secretion and NOS isoenzymes activities was also studied. The inhibitory action of ghrelin on GSIS and the stimulatory effect on the glucagon secretion was accompanied by an increased ncNOS activity. However, such effects of ghrelin were only observed at slightly higher and supra-physiological concentrations (in vitro study). Furthermore, TPN-animals displayed extreme low plasma and tissue levels of ghrelin. Thus, ghrelin does not seem to have any significant role in the reduced GSIS and iNOS expression seen during TPN-treatment. Taken together the data suggest that, besides trauma, hyperglycaemia and hyprelipidemia are able to induce pathophysiological changes in pancreatic islets (iNOS expressing and reduced GSIS) implicating that the nutritional state should be regarded as an important factor for the normal function of islets.
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| 13. |
- Qader, Saleem, et al.
(författare)
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Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: A study on isolated islets from mouse and rat pancreas.
- 2008
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 146:1-3, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- Proghrelin, the precursor of the orexigenic and adipogenic peptide hormone ghrelin, is synthetized in endocrine (A-like) cells in the gastric mucosa. During its cellular processing, proghrelin gives rise to the 28-amino acid peptide desacyl ghrelin, which after octanoylation becomes active acyl ghrelin, and to the 23-amino acid peptide obestatin, claimed to be a physiological opponent of acyl ghrelin. This study examines the effects of the proghrelin products, alone and in combinations, on the secretion of insulin, glucagon, pancreatic polypeptide (PP) and somatostatin from isolated islets of mice and rats. Surprisingly, acyl ghrelin and obestatin had almost identical effects in that they stimulated the secretion of glucagon and inhibited that of PP and somatostatin from both mouse and rat islets. Obestatin inhibited insulin secretion more effectively than acyl ghrelin. In mouse islets, acyl ghrelin inhibited insulin secretion at low doses and stimulated at high. In rat islets, acyl ghrelin inhibited insulin secretion in a dose-dependent manner but the IC50 for the acyl ghrelin-induced inhibition of insulin release was 7.5 × 10− 8 M, while the EC50 and IC50 values, with respect to stimulation of glucagon release and to inhibition of PP and somatostatin release, were in the 3 × 10− 12–15 × 10− 12 M range. The corresponding EC50 and IC50 values for obestatin ranged from 5 × 10− 12 to 20 × 10− 12 M. Desacyl ghrelin per se did not affect islet hormone secretion. However, at a ten times higher concentration than acyl ghrelin (corresponding to the ratio of the two peptides in circulation), desacyl ghrelin abolished the effects of acyl ghrelin but not those of obestatin. Acyl ghrelin and obestatin affected the secretion of glucagon, PP and somatostatin at physiologically relevant concentrations; with obestatin this was the case also for insulin secretion. The combination of obestatin, acyl ghrelin and desacyl ghrelin in concentrations and proportions similar to those found in plasma resulted in effects that were indistinguishable from those induced by obestatin alone. From the data it seems that the effects of endogenous, circulating acyl ghrelin may be overshadowed by obestatin or blunted by desacyl ghrelin.
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| 14. |
- Qader, Saleem
(författare)
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The Role of Nitric Oxide Synthase in Post-Operative Hyperglycaemia
- 2008
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Ingår i: Libyan Journal of Medicine. - 1993-2820. ; 3:3, s. 144-147
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Forskningsöversikt (refereegranskat)abstract
- Post-operative hyperglycaemia is important with regard to outcomes of surgical operations. It affects postoperative morbidity, length of hospital stay, and mortality. Poor peri-operative blood glucose control leads to a higher risk of post-operative complication. Insulin resistance as a cause of post-operative hyperglycaemia has been blamed for some time. Nitric Oxide (NO) is produced by nitric oxide synthase (NOS) isoenzymes. Inducible nitric oxide synthase (iNOS) is not a normal cellular constitute. It is expressed by cytokines and non-cytokines e. g. fasting, trauma, intravenous glucose, and lipid infusion, which are encountered in surgical operations. Review of current published data on postoperative hyperglycaemia was completed. Our studies and others were explored for the possible role of NO in this scenario. Induction and expression of iNOS enzyme in pancreatic islet cells is included in the chaotic postoperative blood glucose control. The high concentrations of iNOS derived NO are toxic to pancreatic beta-cells and may inhibit insulin secretion postoperatively. Hence, current peri-operative management is questionable regarding post-operative hyperglycaemia and necessitates development of a new strategy.
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| 15. |
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| 16. |
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| 17. |
- Salehi, S Albert, et al.
(författare)
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Pulses of somatostatin release are slightly delayed compared with insulin and antisynchronous to glucagon
- 2007
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 144:1-3, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- It was early proposed that somatostatin-producing delta-cells in pancreatic islets have local inhibitory effects on the release of insulin and glucagon. Recent observations that pulses of insulin and glucagon are antisynchronous make it important to examine the temporal characteristics of glucose-induced somatostatin release. Analysis of 30 s fractions from the perfused rat pancreas indicated that increase of glucose from 3 to 20 mmol/l results in initial suppression of somatostatin release followed by regular 4-5 min pulses. During continued exposure to 20 mmol/l glucose, the pulses of somatostatin overlapped those of insulin with a delay of 30 s. Somatostatin and glucagon pulses were coupled in antisynchronous fashion (phase shift 2.4 +/- 0.2 min), supporting the idea that the delta-cells have a local inhibitory effect on glucagon release. It was possible to remove the pulses of somatostatin and glucagon with maintenance of the insulin rhythmicity by addition of I mu mol/l of the P2Y(1) receptor antagonist MRS 2179.
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