Search Results

You are looking at 1 - 8 of 8 items for

  • Author: Jens F Rehfeld x
  • All content x
Clear All Modify Search
Restricted access

Jens F. Rehfeld

ABSTRACT

The effect of intravenous injection of gastrin and its C-terminal tetrapeptide amide (tetragastrin) on insulin secretion was studied in ten normal young men. Each subject was given 150 Leo-units (150 μg) of tetragastrin on one occasion and on another, 150 Leo-units of hog gastrin. Tetragastrin administration resulted in a definite increase in the concentration of immunoreactive insulin in all subjects, while the gastrin injection induced a slight insulin response in only six of the ten subjects. Thus, in a biological test on the effect of the gastrins, tetragastrin was found to be more potent than gastrin.

Restricted access

Linda Bardram, Jörgen Lindholm, and Jens F. Rehfeld

Abstract. Twelve of 87 pituitary adenomas from patients with acromegaly, Cushing's syndrome, Nelson's syndrome, hyperprolactinaemia and without symptoms of hormone hypersecretion contained gastrin in concentrations from 0.5 to 166 pmol/g. Only ACTH-producing tumours contained gastrin, which occurred in forms smaller than those present in the normal adenohypophysis. The results indicate that corticotropic tumours may synthesize gastrin in moderate amounts.

Restricted access

Linda Bardram, Linda Hilsted, and Jens F. Rehfeld

Abstract. Using sequence-specific radioimmunoassays before and after cleavage with trypsin and carboxypeptidase B, we have examined the occurrence and molecular nature of cholecystokinin (CCK) and gastrin peptides in bioactive (i.e. α-carboxyamidated) as well as non-amidated precursor forms in extracts from 13 human pheochromocytomas. All but one tumour contained amidated CCK, but only in moderate amounts (≤ 20 pmol/g tissue). In contrast to the complete sulphation in tissues which normally produce CCK (the brain and small intestine), the amidated adrenal CCK peptides were poorly sulphated (≤ 17%). Four pheochromocytomas, including the one without amidated CCK, contained between 28 and 0.2 pmol amidated gastrin/g, mainly in the form of sulphated gastrin-17. In addition, all tumours contained biosynthetic precursors of both CCK and gastrin. In most extracts there was more precursor than bioactive peptide(s), the progastrin concentration ranging up to 338 pmol/g. The results show that pheochromocytomas synthesize CCK and gastrin. The posttranslational processing differs, however, markedly from that of the principal CCK and gastrin producing tissues, with respect to both proteolytic cleavages and amino acid derivatization. This emphasizes that accurate quantitation in tumours requires assays which measure the translation products irrespective of their degree of processing.

Restricted access

Lars Ødum, Julie Pildal, and Jens F Rehfeld

Ødum L, Pildal I. Rehfeld pJF. Somatostatin in the boar reproductive system. Eur J Endocrinol 1994;130:515–21. ISSN 0804–4643

Somatostatin (SRIF) is a widely distributed regulatory peptide. Recently, it was shown that human seminal plasma contains high concentrations of SRIF. In order to find the cellular source of seminal SRIF we have examined the presence of SRIF in porcine urogenital tissues. The concentration of SRIF in male accessory reproductive tissues of 3-month-old pigs (N = 4) ranged from 1 to 17 nmol/kg. In the boar, only the prostate gland contained significant amounts of SRIF (median 7 nmol/kg, range 3–18 nmol/kg, N = 4). Testis and semen contained no SRIF. Gel chromatography of extracts of the male accessory sex glands and epididymis showed both SRIF-28 and SRIF-14, whereas urinary bladder contained mainly SRIF-14. In conclusion, the results show a considerable species, tissue and developmental variation in the expression of SRIF in the genitourinary tract.

Lars Ødum, Department of Clinical Chemistry, Herlev Hospital, Herlev Ringvej 75, DK-2730, Denmark

Restricted access

Jan Fahrenkrug, Ove B. Schaffalitzky de Muckadell, and Jens F. Rehfeld

ABSTRACT

The serum concentrations of immunoreactive gastrin and immunoreactive calcitonin were measured in 13 fasting patients with achlorhydria and pernicious anaemia and in 10 age- and sex-matched fasting control subjects. All patients had highly elevated concentrations of gastrin in serum (1486 ± 336 pg/ml, mean ± sem). The mean concentration in the controls was 35.2 ± 6.4 pg/ml. No difference in the concentration of calcitonin was found between the pernicious anaemia patients and the controls, the levels being 0.93 ± 0.08 and 0.89 ± 0.03 ng/ml, respectively. Suppression of endogenous gastrin secretion in 5 of the patients by intragastric acid administration was not accompanied by any decrease in calcitonin concentration in serum.

The findings suggest that chronically elevated endogenous gastrin is without influence on calcitonin secretion.

Free access

David P Sonne, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, and Filip K Knop

Objective

Recent preclinical work has suggested that postprandial flow of bile acids into the small intestine potentiates nutrient-induced glucagon-like peptide 1 (GLP1) secretion via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells. The notion of bile-induced GLP1 secretion combined with the findings of reduced postprandial gallbladder emptying in patients with type 2 diabetes (T2DM) led us to speculate whether reduced postprandial GLP1 responses in some patients with T2DM arise as a consequence of diabetic gallbladder dysmotility.

Design and methods

In a randomised design, 15 patients with long-standing T2DM and 15 healthy age-, gender- and BMI-matched control subjects were studied during 75-g oral glucose tolerance test (OGTT) and three isocaloric (500 kcal) and isovolaemic (350 ml) liquid meals: i) 2.5 g fat, 107 g carbohydrate and 13 g protein; ii) 10 g fat, 93 g carbohydrate and 11 g protein; and iii) 40 g fat, 32 g carbohydrate and 3 g protein. Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP1, glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin and gastrin were measured. Furthermore, gallbladder emptying and gastric emptying were examined.

Results

Gallbladder emptying increased with increasing meal fat content, but no intergroup differences were demonstrated. GIP and GLP1 responses were comparable among the groups with GIP levels being higher following high-fat meals, whereas GLP1 secretion was similar after both OGTT and meals.

Conclusions

In conclusion, patients with T2DM exhibited normal gallbladder emptying to meals with a wide range of fat content. Incretin responses were similar to that in controls, and an association with postprandial gallbladder contraction could not be demonstrated.

Free access

Solrun Vidarsdottir, Ferdinand Roelfsema, Trea Streefland, Jens J Holst, Jens F Rehfeld, and Hanno Pijl

Background

Treatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth, might cause less weight gain than olanzapine standard oral tablets (OST).

Design and methods

Ten healthy men received olanzapine ODT (10 mg o.d., 8 days), olanzapine OST (10 mg o.d., 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, blood samples were taken for measurement of pancreatic polypeptide, peptide YY, glucagon-like peptide-1, total glucagon, total ghrelin, and cholecystokinin (CCK) concentrations.

Results

With the exception of pre- and postprandial concentration of ghrelin at dinner and preprandial CCK concentrations at breakfast, which were all slightly increased (respectively P=0.048, P=0.034 and P=0.042), olanzapine did not affect gut hormone concentrations. Thus, olanzapine ODT and OST had similar effects on gut hormone secretion.

Conclusion

Short-term treatment with olanzapine does not have major impact on the plasma concentration of gut hormones we measured in healthy men. Moreover, despite pharmacological difference, gut hormone concentrations are similar during treatment with olanzapine ODT and OST. The capacity of olanzapine to induce weight gain and diabetes is unlikely to be caused by modulation of the secretion of gut hormones measured here. We cannot exclude the possibility that olanzapine's impact on other gut hormones, to impair insulin sensitivity and stimulate weight gain, exists.

Restricted access

Niels B Dalsgaard, Lærke S Gasbjerg, Laura S Hansen, Nina L Hansen, Signe Stensen, Bolette Hartmann, Jens F Rehfeld, Jens J Holst, TIna Vilsbøll, and Filip K Knop

Aims: The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes.

Methods: In a double-blinded, placebo-controlled, randomised, crossover study, 15 participants with metformin-treated type 2 diabetes (Age 57-85 years, HbA1c 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a six-week wash-out period. At the end of each period, two randomised 4-hour liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed.

Results: Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± SD) during exendin(9-39)NH2 infusion in the acarbose period vs. a 39 ± 27% increase during the placebo period (p = 0.0163).

Conclusions: We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.