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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impaired epinephrine and glucagon responses to hypoglycemia often found in patients with insulin-dependent diabetes mellitus (IDDM) may be due to autonomic neuropathy. Since the pancreatic polypeptide response to hypoglycemia is mediated by cholinergic mechanisms, we used this response as an indicator of autonomic neuropathy to determine whether deficient epinephrine and glucagon responses in IDDM could be ascribed to an autonomic defect. The relationships between pancreatic polypeptide, epinephrine, and glucagon responses during insulin-induced hypoglycemia were assessed in 18 patients with IDDM who had no overt evidence of autonomic neuropathy, including normal standard cardiovascular reflex tests, and 11 age-matched nondiabetic subjects. All of the diabetic patients had impaired glucagon responses [19 +/- 3 (SEM) vs. 96 +/- 11 pg/ml, peak increment, P less than 0.001]. Ten of the 18 diabetic patients had either impairment of plasma epinephrine or plasma pancreatic polypeptide responses or both to hypoglycemia. Moreover, pancreatic polypeptide responses were significantly correlated with epinephrine responses (r = 0.53, P less than 0.003). There was no association between the plasma glucagon response and the epinephrine (r = 0.02, NS), norepinephrine (r = 0.03, NS), or pancreatic polypeptide (r = 0.35, NS) response. Last, there was no correlation between the plasma hormone responses and the cardiovascular reflex test results. Therefore, the association of impaired plasma pancreatic polypeptide responses with impaired plasma epinephrine responses suggests that the impaired epinephrine responses are due to autonomic neuropathy, whereas the dissociation of plasma glucagon responses with both plasma pancreatic polypeptide and epinephrine responses suggests that the impaired pancreatic alpha-cell response to hypoglycemia is not due to autonomic neuropathy. In addition, the plasma pancreatic polypeptide and epinephrine responses to hypoglycemia appear to be an earlier indicator of underlying autonomic dysfunction than standard cardiovascular reflex tests. Thus, the responses of plasma pancreatic polypeptide and epinephrine to insulin-induced hypoglycemia may be a useful test for the identification of early autonomic neuropathy in IDDM.
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PMID:The significance of impaired pancreatic polypeptide and epinephrine responses to hypoglycemia in patients with insulin-dependent diabetes mellitus. 381 92

A 66 year old patient with diabetes had a necrolytic migratory erythema, weight loss and anaemia. Plasma immunoreactive glucagon (IRG) of 2465 pmoles/l (normal 35 +/- 5 SEM pmoles/l) suggested the existence of a glucagonoma which was confirmed by arteriography and subsequently removed by surgery. Although plasma IRG returned to normal, glucose tolerance and insulin secretion remained pathological. Plasma amino acid levels had been reduced but were corrected by surgery. Pancreatic polypeptide, however, 298 pmoles/l before was still 206 pmoles/l after the operation (normal 12-48 pmoles per litre). Column chromatography of plasma and tumor extracts showed quantitatively important IRG fractions with molecular weights above 9000 daltons, possibly precursors of glucagon. Beside a 50-fold IRG excess, the tumour concentrations of insulin and somatostatin were 4 to 150 times increased. By contrast, pancreatic polypeptide was present in normal amounts. Electron microscopic examination showed atypical A-cell granula and unusual abundance of mitochondria.
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PMID:In vitro and in vivo studies on glucagonoma tissue. 610 27

To determine the effect of the 75 g oral glucose tolerance test on carbohydrate and lipid metabolism, the splanchnic exchange of glucose, lactate, pyruvate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate as well as the release of insulin, C-peptide, glucagon and pancreatic polypeptide were evaluated in eight healthy male volunteers in the basal state and for 150 min following glucose ingestion. Oral glucose loading was followed by a rapid rise in splanchnic output of glucose (mean +/- SEM; 154 +/- 12 mmol/150 min), pyruvate (1.2 +/- 1.2 mmol/150 min) and lactate (8.6 +/- 2.0 mmol/150 min), whereas there were reductions in the splanchnic uptake of non-esterified fatty acids (-10.7 +/- 4.4 mmol/150 min) and the splanchnic output of beta-hydroxybutyrate (-4.8 +/- 3.3 mmol/150 min) and acetoacetate (-3.0 +/- 1.2 mmol/150 min). In parallel, splanchnic output of insulin (12.3 +/- 2.7 nmol/150 min), C-peptide (36.1 +/- 5.0 nmol/150 min) and transiently of pancreatic polypeptide rose, whereas that of glucagon fell (-0.58 +/- 0.21 nmol/150 min). Even at 150 min after glucose ingestion, splanchnic output and arterial concentrations of glucose, lactate, insulin and C-peptide were still above their respective basal values while those of non-esterified fatty acids and glucagon were reduced. Taking into account the partial suppression of endogenous glucose production by ingested glucose it is concluded that, in normal postabsortive man, only 49-63% of a 75 g oral glucose load is retained by the splanchnic bed during the first 150 min, the rest being available for non-hepatic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 75-g oral glucose tolerance test: effect on splanchnic metabolism of substrates and pancreatic hormone release in healthy man. 636 76

Secretion of pancreatic polypeptide (PP) is regulated mainly by cholinergic mechanisms and we have studied this in patients with chronic renal failure (CRF). Basal serum PP concentrations in 25 patients with CRF (401 +/- 80; 116-2100 pmol/l; mean +/- SEM and range) were significantly higher than in 65 normal subjects (33 +/- 2; 21-120 pmol/l, P less than 0.001). Ingestion of a standard test meal induced significantly larger increases in serum PP in 11 patients with CRF (304 +/- 45; 155-640 pmol/l) than in 11 normal subjects (140 +/- 33; 51-440 pmol/l, P less than 0.005). Insulin-hypoglycaemia (0.1 U/kg i.v.) provoked similar increases in serum PP in five patients with CRF (404 +/- 79; 170-665 pmol/l) as in five normal subjects (449 +/- 92; 180-706 pmol/l). Administration of atropine (1 mg i.v.) did not normalize the elevated basal serum PP concentrations in five patients with CRF. On the other hand, administration of the same dose of atropine 60 min after ingestion of food decreased postprandial serum PP levels to basal values within one hour both in five patients with CRF and in six normal subjects. Sephadex G-50 column chromatography of basal, postprandial and post-atropine sera from three patients with CRF revealed at least three different molecular forms. The PP peak coeluting with the 4200 molecular weight human PP standard comprised more than half of total PP immunoreactivity and was the only peak to be influenced by feeding or atropine. We conclude that in patients with CRF, PP secretion stimulated by cholinergic mechanisms is normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholinergic regulation of pancreatic polypeptide secretion in chronic renal failure. 637 35

Prostaglandins and prostaglandin synthesis inhibitors are known to influence the secretion of a number of hormones. More specifically, sodium salicylate is known to increase insulin secretion in Type II diabetics in response to a glucose stimulus. To challenge the hypothesis that prostaglandins may be instrumental in a generalized defect of glucose recognition in Type II diabetics, the effect of sodium salicylate on the hormonal counter-regulatory response to insulin-induced hypoglycaemia was examined. Before salicylate treatment, seven Type II diabetics had brisk increases (mean +/- SEM) in circulating adrenaline (time 0 = 50 +/- 7 pg/ml; peak = 1630 +/- 330 pg/ml), noradrenaline (time 0 = 260 +/- 46 pg/ml; peak = 770 +/- 140 pg/ml), glucagon (time 0 = 38 +/- 6 pg/ml; peak = 75 +/- 10 pg/ml) and pancreatic polypeptide (time 0 = 149 +/- 30 pg/ml; peak = 1170 +/- 180 pg/ml) in response to insulin-induced hypoglycaemia. In contrast to previous studies in normal subjects, treatment with sodium salicylate failed to augment hypoglycaemia-induced secretion of adrenaline, noradrenaline or pancreatic polypeptide in Type II diabetics. The glucagon response to hypoglycaemia was augmented by sodium salicylate when the data were expressed as the incremental area under the glucagon vs. time curve, but not when peak response was used for analysis. These results are inconsistent with a prostaglandin-related generalized defect in glucose recognition in Type II diabetics and suggest that augmentation of hormone secretion in these patients by sodium salicylate may be specific for glucose-induced insulin secretion.
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PMID:Effect of sodium salicylate on hormonal responses to hypoglycaemia in type II diabetics. 639 45

Neurotensin (NT) is a 13 amino acid peptide found predominantly in the ileum and it is released into the circulation by a meal. Much of the circulating NT consists of N terminal fragments which have no known biological activity. However, the sites and rates of NT metabolism are not known. In the present study the MCR and half-disappearance time of NT were estimated by infusing NT(1-13) into 10 normal subjects. The role of the kidney was assessed by studies in patients with chronic renal failure (CRF). The nature of the metabolites was characterized using region specific antisera and high pressure liquid chromatography (HPLC). The plasma pancreatic polypeptide response to the NT infusion was also measured. The NT MCR in normal subjects was 88 +/- 25 (SEM) ml/min X kg measured with the C terminal antiserum but only 9.9 +/- 0.8 ml/min X kg measured with the N terminal antiserum, a result consistent with the presence of long lasting N terminal fragments. HPLC of the plasma at equilibrium established that only 20% of the immunoreactivity was present as NT(1-13), with the majority as NT(1-8). No C terminal fragment were detected. Similarly, incubation of NT(1-13), 1-8, and 8-13 in plasma in vitro showed that N terminal fragments were stable in plasma, whereas C terminal fragments were completely metabolized. In patients with CRF, basal plasma NT (measured with the C terminal antisera) was significantly elevated and C terminal MCR was reduced by 82% and N terminal MCR by 32%. Thus the major effect of CRF was on the initial degradation of NT(1-13) to N terminal fragments. HPLC showed that over 60% of the NT was present as NT(1-13). In vitro degradation of NT was also slowed in CRF plasma. The increased proportion of intact biologically active NT in the circulation of the CRF patients could also explain the greater increase in pancreatic polypeptide levels during the NT(1-13) infusion. These studies have established that the metabolism of NT is influenced by the kidney and that the presence of predominantly N terminal fragments of NT in the peripheral circulation of normal subjects can be explained by a combination of renal and extrarenal factors.
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PMID:Metabolism of neurotensin and pancreatic polypeptide in man: role of the kidney and plasma factors. 670 91

Gastrin-releasing peptide (GRP) was infused at two dose levels [GRP I (0-30 min): bolus dose of 1.41 pmol kg-1, followed by 0.12 pmol kg-1 min-1; GRP II (30-60 min): bolus dose of 5.67 pmol kg-1, followed by 1.50 pmol kg-1 min-1] to six normal men to study the pharmacokinetics of GRP using a newly developed RIA and the effect of GRP on gastro-entero-pancreatic hormones and gastric acid secretion. The half-life of disappearance of GRP was 2.8 +/- 0.4 min (+/- SEM). The MCR and the apparent space of distribution were 33.0 +/- 4.0 ml kg-1 min-1 and 133 +/- 31 ml kg-1, respectively. GRP stimulated the secretion of gastrin, pancreatic polypeptide, insulin, glucagon, and glucose-dependent insulinotropic polypeptide in a dose-dependent manner. Gastric acid secretion was stimulated 15 min after the increase in gastrin secretion, suggesting that GRP stimulated gastric acid secretion via release of gastrin. GRP had no significant effect on the secretion of enteroglucagon or neurotensin. In the mammalian gastrointestinal tract, GRP is localized exclusively to nerve tissue. This fact and its potent effects demonstrated here make it a likely candidate for peptidergic nervous control of gastrointestinal function.
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PMID:Gastrin-releasing peptide: pharmacokinetics and effects on gastro-entero-pancreatic hormones and gastric secretion in normal men. 673 5

Pancreatic polypeptide was infused intravenously in healthy fasting subjects at 1 pmol kg-1 (n = 7) and 4 pmol kg-1 min-1 (n = 10) producing plasma PP concentrations of 223 +/- 37 pmol/l (mean +/- SEM) and 891 +/- 64 pmol/l respectively. These levels are similar to and four-fold higher than those seen after a normal mixed breakfast in healthy young adults. In a separate study five healthy subjects ingested a small breakfast during infusion of PP on different days at 1 pmol kg-1 min-1 and 2 pmol kg-1 min-1 respectively. PP at 1 pmol kg-1 min-1 caused a marked reduction in fasting plasma motilin concentrations to 20% of the basal level (p less than 0.001). There were, however, no significant changes in plasma concentrations of insulin, glucagon, gastrin, secretin, enteroglucagon, gastric inhibitory peptide or neurotensin. Despite previous reports possibly implicating PP in metabolism, there were no significant effects on blood levels of glucose, alanine lactate, 3-hydroxybutyrate, glycerol or non-esterified fatty acids, either in the fasting state or after the ingestion of food. Although it seems unlikely that PP is a major hormonal regulator of intermediary metabolism in man, its ability to suppress motilin at physiological concentrations suggests the possibility of an indirect influence on digestive motor function.
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PMID:Effects of pancreatic polypeptide on motilin and circulating metabolites in man. 678 20

The plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP), gut glucagon-like-immunoreactivity (gut GLI), insulin, glucagon, and pancreatic polypeptide (PP) were studied following the ingestion of a protein rich meal in late pregnancy and postpartum in 11 normal women. In pregnancy, the fasting plasma concentrations of glucose (mean +/- SEM in pregnancy: 4.1 +/- 0.1 mmol l-1, postpartum: 4.7 +/- 0.1 mmol l-1, P less than 0.01), gut GLI (25 +/- 3 v. 33 +/- 2 pmol-eqv l-1, P less than 0.01), and PP (7.9 +/- 1.0 v. 13.0 +/- 1.2 pmol l-1, P less than 0.01) were decreased, gastrin and GIP unaltered, and insulin (90 +/- 9 v. 72 +/- 5 pmol l-1, P less than 0.05) and glucagon (17 +/- 1 v. 13 +/- 1 pmol l-1, P less than 0.01) increased. The gastrin, GIP and glucagon responses to the meal were unaffected by pregnancy, whereas the responses of gut GLI (integrated responses in pregnancy: 1217 +/- 325 pmol-eqv l-1, postpartum 2223 +/- 404 pmol-eqv l-1, P less than 0.05) and PP (9801 +/- 1440 v. 14,078 +/- 1543 pmol l-1, P less than 0.01) were impaired and the insulin response enhanced (27,973 +/- 6814 v. 11,409 +/- 3102 pmol l-1, P less than 0.01) in pregnancy. The physiological implications of these findings are at present not known in detail. They may, however, be important for the altered carbohydrate metabolism in pregnancy and also for the changes occurring during gestation in gastrointestinal physiology.
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PMID:Gastro-entero-pancreatic hormones in normal pregnancy: response to a protein rich meal. 680 Aug 4

The hemodynamic, hormonal and electrolyte effects of prenalterol, a synthetic selective beta 1 agonist, were studied in six patients with New York Heart Association functional class II and III heart failure. Prenalterol was infused incrementally at 60, 120 and 240 nmol/min, each rate for 24 hours, producing steady-state plasma prenalterol levels of 52 +/- 3, 121 +/- 6 and 194 +/- 9 nmol/1, respectively (mean +/- SEM). Hemodynamic and hormonal measurements were performed before, during and after prenalterol administration under conditions of constant body posture and a regulated intake of dietary sodium and potassium. Prenalterol induced a statistically significant increase in cardiac index (from 2.6 +/- 0.2 to 3.1 +/- 0.3 1/min/m2), with parallel increases in stroke index (from 28 +/- 2 to 34 +/- 2 ml/beat/m2). Forearm blood flow measurements increased (from 2.9 +/- 0.5 to 4.1 +/- 0.6 ml/min/100 g), while calculated systemic vascular resistance fell, as did pulmonary capillary wedge pressure (from 13.7 +/- 1.6 to 10.5 +/- 1.7 mm Hg). The drug did not alter heart rate, arterial pressure, right heart pressures or the frequency of ventricular premature beats. Prenalterol increased plasma renin activity (from 2.9 +/- 0.8 to 6.6 +/- 1.8 nmol/1/hour), angiotensin II (from 59 +/- 12 to 89 +/- 22 pmol/1), urinary aldosterone excretion (from 41 +/- 10 to 78 +/- 34 nmol/day) and plasma insulin (from 10.6 +/- 2.2 to 19.8 +/- 3.9 mU/1). Circulating catecholamines, cortisol, glucose, glucagon or pancreatic polypeptide did not change. Dose-response studies in five patients showed dose-dependent increments in hemodynamic variables, while hormonal changes plateaued at the second dose level. We conclude that prenalterol infusion augments myocardial contractility, reduces systemic vascular resistance, and stimulates insulin release and the renin-angiotensin-aldosterone system.
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PMID:Hemodynamic, hormonal and electrolyte responses to prenalterol infusion in heart failure. 682 3


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