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Biomedical subjects

T Krarup

Publications and source records attributed to T Krarup.

At least 91 records · Page 5Linked to original sources

The effect of insulin deprivation on fasting levels of 5000 dalton gastric inhibitory polypeptide in type 1 (insulin-dependent) diabetics.

To investigate whether metabolic decompensation has an effect on gastric inhibitory polypeptide (GIP), 8 fasting male type 1 diabetics were deprived of insulin for 12 h. An overnight insulin infusion aiming at normoglycaemia was stopped at 08.00 h. During the following 12 h blood glucose increased from 7.0 +/- 0.4 to 14.9 +/- 1.0 mmol/l, P less than 0.01, 3-hydroxy-butyrate from 0.18 +/- 0.07 to 4.00 +/- 0.74 nmol/1, P less than 0.01, and immunoreactive GIP (IR-GIP) from 16.7 +/- 2.6 to 21.9 +/- 2.9 pmol/1, P less than 0.05. The antiserum employed, R65, only measures 5000 dalton IR-GIP. The final IR-GIP concentrations were not significantly different from fasting IR-GIP concentrations in 13 normal male subjects (17.4 +/- 1.5 pmol/1). Short term insulin deprivation therefore is associated with a slight increase in fasting IR-GIP concentrations. Whether this modest increase in IR-GIP significantly enhances insulin secretion is unknown.

3-Hydroxybutyric Acid↗

Gastroenteropancreatic hormones in normal and gestational-diabetic pregnancy: response to oral lipid.

The effect of normal and gestational-diabetic pregnancy on the gastroenteropancreatic (GEP) hormone response to lipid ingestion was studied in 17 women, 8 normal and 9 with gestational diabetes, by determination of the plasma concentrations of gastric inhibitory polypeptide (GIP), gut glucagon-like immunoreactivity (gut GLI), insulin, glucagon, and pancreatic polypeptide (PP) following the ingestion of 67 g of triglyceride in late pregnancy and postpartum. Also, the plasma concentrations of free fatty acids (FFA), triglyceride, and glucose were determined. In both groups fasting plasma triglyceride and insulin were increased and PP was decreased. Fasting plasma glucose and gut GLI were decreased in normal pregnancy, but were unaltered in gestational-diabetic pregnancy. Fasting plasma glucagon were unaltered in normal but increased in gestational diabetic pregnancy. In both groups of women the GIP response to triglycerides was impaired in pregnancy. Postpartum, the GIP response was greater in the gestational diabetics than in normal women whereas no difference was found in pregnancy. The other hormones and metabolites responded similarly in pregnancy and postpartum and no difference between normal women and women with gestational diabetes was found. It is concluded that the GIP response to triglycerides is impaired in pregnancy.

Adult↗

The heterogeneity of gastric inhibitory polypeptide in porcine and human gastrointestinal mucosa evaluated with five different antisera.

The Sephadex G-50 gel filtration profile of immunoreactive gastric inhibitory polypeptide (GIP) in porcine and human gastrointestinal mucosa was determined in assays with antisera obtained from five different groups working with GIP. Tissue was extracted in acid ethanol or using a boiling method. Three well-defined components were detected with three of the antisera: one component corresponding to natural porcine GIP (5 kDa GIP), one component corresponding to what has been called 8 kDa GIP, and one component somewhat larger than the latter. One antiserum did not measure 8 kDa GIP at all, while the fifth antiserum measured small amounts of 8 kDa GIP in porcine but not in human extracts. While the antisera measured the same amounts of GIP in porcine extracts, two of the antisera measured significantly more GIP than the remaining three in extracts of human mucosa. The elution position of human 5 kDa GIP differed significantly from that of porcine 5 kDa GIP. In addition to the identification of a new molecular form of GIP, and the demonstration of important specificity differences among GIP antisera currently in use, the present results indicate that human and porcine 5 kDa GIP differ in chemical composition.

Animals↗

Gastrin-releasing peptide: pharmacokinetics and effects on gastro-entero-pancreatic hormones and gastric secretion in normal men.

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.

Adult↗

Relation of immunoreactive gastric inhibitory polypeptide to changes in glycaemic control and B cell function in type 1 (insulin-dependent) diabetes mellitus.

The effect of strict glycaemic control on plasma immunoreactive gastric inhibitory polypeptide (IR-GIP) concentrations and pancreatic B cell function as estimated by plasma C-peptide was evaluated in 14 Type 1 (insulin-dependent) diabetics. The effect was estimated by giving a test meal before (test 1) and after (test 2) 1 week with near normal blood glucose control (mean blood glucose 6.7 +/- 0.2 mmol/l) and again 3 weeks later (test 3) in the outpatient clinic. The glycaemic control was significantly improved at test 2 and test 3 compared with that of test 1. The IR-GIP concentrations before and after the meals were similar at all three tests and not different from those found in 21 normal controls. In 8 patients with a significant B cell response at test 1, B cell function was significantly improved both at test 2 and test 3 but no change in fasting or post-prandial IR-GIP concentrations was found and no correlation between B cell function and IR-GIP existed. We conclude that strict glycaemic control improves B cell function but does not modulate plasma IR-GIP concentrations. Factors other than GIP seem to be of greater importance in determining the magnitude of B cell function in Type 1 diabetes.

Adolescent↗

Herald lesion of the urinary bladder.

The herald lesion of the urinary bladder is defined as an unspecific localized cystitis, eventually polypoid, in patients with symptoms from the lower urinary tract. The herald lesion is visualized by cystoscopy. Biopsies from the lesion show unspecific acute and/or chronic inflammation often accompanied by hyperplasia of the transitional cell epithelium. The herald lesion portends a neoplastic or inflammatory process in neighbouring organs. At our Institute of Pathology fourteen cases of the herald lesion were diagnosed during one and a half years. In 113 consecutive patients with ulcerative colitis and Crohn's disease no case of the herald lesion was found.

Adult↗

Lack of negative feed-back regulation of insulin on the responses of gastric inhibitory polypeptide, insulin, glucagon and pancreatic polypeptide to a meal in insulin treated diabetics.

The effect of insulin on the secretion of immunoreactive gastric inhibitory polypeptide, insulin (as measured by C-peptide), glucagon and pancreatic polypeptide during and after a test meal was examined in seven diabetic patients treated with high insulin doses (mean 1.12 +/- 0.12 IU/kg X 24 h) before and after a reduction of the insulin dose (to 0.62 +/- 0.04 IU/kg X 24 h, p less than 0.02). While plasma insulin concentrations were significantly higher on the higher dose, no significant differences were found in the responses of immunoreactive gastric inhibitory polypeptide, C-peptide, glucagon and pancreatic polypeptide to the two meals. Blood glucose concentrations were not significantly different at the two tests. It thus seems that insulin has no direct effect on the secretion of these substances after a meal in insulin-treated diabetics.

Adult↗

Plasma somatostatin increases during hypoglycaemia in insulin-dependent patients with and without B-cell function.

Responses of somatostatin-like immunoreactivity (SLI) to hypoglycaemia were investigated in seven type 1 (insulin-dependent) patients with residual B-cell function, eight patients without B-cell function, and six healthy controls. A higher basal level of SLI was found in the group with B-cell function when compared with the group without B-cell function. The basal level in the normal subjects was in between the two diabetic groups. All the diabetics had a somatostatin response to hypoglycaemia which was independent of residual B-cell function and no different from that of normal subjects.

Adolescent↗

Response of pancreatic polypeptide to hypoglycaemia in insulin-dependent diabetics with and without residual beta-cell function.

To investigate a possible association between the beta-cells and the cells secreting pancreatic polypeptide (PP), the response of PP to insulin-induced hypoglycaemia was investigated in seven insulin-dependent diabetics with and seven without residual beta-cell function, all without signs of autonomic neuropathy. The mean concentrations of PP was significantly greater from 15 to 60 min after symptoms of hypoglycaemia in patients with residual beta-cell function than in patients without (P less than 0.05) despite similar blood glucose concentrations in the two groups. Also the total integrated areas beneath the response curves as well as the incremental integrated areas were significantly greater in patients with beta-cell function (216 +/- 36 pmol/l x min and 188 +/- 34 pmol/l x min, respectively) than in patients without beta-cell function (125 +/- 26 pmol/l x min and 102 +/- 26 pmol/l x min) (P less than 0.05 for both). The mean maximal concentrations of adrenaline (1.53 +/- 0.28 ng/ml v. 1.29 +/- 0.12 ng/ml) and noradrenaline (0.56 +/- 0.16 ng/ml v. 0.45 +/- 0.04 ng/ml) were not statistically different in the two groups. No well established explanation for an association between residual insulin secretion and capacity for PP-response to hypoglycaemia in type 1 diabetics exists.

Adult↗

Diminished immunoreactive gastric inhibitory polypeptide response to a meal in newly diagnosed type I (insulin-dependent) diabetics.

The release of immunoreactive gastric inhibitory polypeptide (IR-GIP) in response to a standard meal was examined in 10 normal subjects and 15 type I (insulin-dependent) diabetics 7 days (test I), 14 days (test II), and 3 months (test III) after time of diagnosis. During all three tests, the diabetics had significantly lower plasma IR-GIP concentrations than the controls from 15-90 min after the standard meal. The IR-GIP response in the diabetics measured as the integrated area under the response curve corresponded to 70% of that of normal subjects. beta-cell function evaluated from the C-peptide response to the meal increased significantly from test I to test III whereas the IR-GIP response was similar during all three tests. As GIP is known to potentiate glucose-induced insulin secretion and possibly the biosynthesis of insulin, the low IR-GIP responses in subjects with type I diabetes may significantly influence insulin levels and hyperglycemia.

Adolescent↗

Urinary flow studies in normal kindergarten--and schoolchildren.

The problems in the evaluation of children with suspected infravesical obstruction are shortly reviewed. Based upon literature studies it is concluded, that an isolated urinary flow measurement determining the Qmax is a suitable procedure of screening. Due to different shortcomings of earlier published normal materials, we investigated the spontaneous urination of 205 normal children aged 3 to 13 years in their normal environment. The mictiograph was installed in the toilet of two kindergartens and one school, enabling the children freely to void into the machine upon desire. From the flow curves the following parameters were calculated: Q1 sec, Qmax, Qmax time, and the micturition time, all of them being related to the square root of the voided volume. The data were non-parametrically statistically processed, and the limits of normal values (2 1/2% and 97 1/2% percentiles) are defined for different groups of age and sex. Furthermore, the different flow curve patterns are described, and it is found, that in 90% of the cases they are identical to the adult pattern.

Adolescent↗

The transient effect of strict glycaemic control on B cell function in newly diagnosed type 1 (insulin-dependent) diabetic patients.

Within 24h of diagnosis, 15 consecutive Type 1 (insulin-dependent) diabetic patients were allocated at random to one of two treatment groups: group A (n = 9, mean age: 28 years, range: 17-35 years) was treated conventionally with one or two daily doses of insulin; group B (n = 6, mean age: 27 years, range: 21-37 years) was treated with nine daily injections of fast-acting insulin for ten days and there-after conventionally as for group A. The mean diurnal blood glucose concentration during the initial ten days of insulin treatment was 11.7 +/- 0.5 mmol/l (mean +/- SEM) in group A and 6.4 +/- 0.3 mmol/l in group B (p less than 0.01). Pancreatic B cell function was evaluated 1, 7, 14, 90, and 180 days after the start of insulin treatment from the C-peptide response to a standard meal. At one and seven days after diagnosis, no difference was found in B cell function between the two groups. After 14 days, the amount of C-peptide secreted during the test meal was 18.0 +/- 2.6 nmol (mean +/- SEM) in group A compared with 29.0 +/- 3.6 nmol in group B (p less than 0.05). After 90 and 180 days, no difference was demonstrated in B cell function. The maximal B cell function observed was similar in the two groups, but occurred earlier in group B (at 14 days) than in group A (at 90 days) (p less than 0.05). This study indicates that strict initial glycaemic control may lead to an earlier improvement in B cell function, but that this improvement is of short duration.

Adolescent↗

Hormonal, metabolic and cardiovascular responses to hypoglycaemia in Type 1 (insulin-dependent) diabetes with and without residual B cell function.

Hormonal, metabolic and cardiovascular responses to insulin induced hypoglycaemia were investigated in seven Type 1 (insulin-dependent) diabetic patients with residual B cell function, eight Type 1 diabetic patients without B cell function and six healthy subjects. No differences were found between the diabetic groups regarding nadir of glucose and rate of recovery to normoglycaemia. The patients with residual B cell function had a glucagon response to hypoglycaemia which was close to that of normal subjects. In patients without B cell function, the glucagon response to hypoglycaemia was present, albeit significantly smaller than in the patients with preserved B cell function (0.025 ng/ml, range 0.007-0.042 versus 0.054 ng/ml, range 0.029-0.087). The group without B cell function had signs of an exaggerated rate of lipolysis and ketogenesis compared with the patients with B cell function and the normal subjects.

Adult↗

B cell function in patients with chronic pancreatitis and its relation to exocrine pancreatic function.

Exocrine pancreatic function was evaluated by a Lundh meal test and a secretin-cholecystokinin test in 16 patients with chronic pancreatitis. B cell function was assessed by measuring the concentration of C-peptide after stimulation with oral glucose and intravenous glucagon. The Cc-peptide response to intravenous glucagon and oral glucose was closely correlated (r = 0.88, p less than 0.01). Plasma C-peptide after glucagon was significantly correlated to the post-prandial concentration of lipase (r = 0.72, p less than 0.001), amylase (r = 0.64, p less than 0.05) and to amylase output (r = 0.64, p less than 0.05). Eight out of nine patients treated with insulin had residual B cell function, but it diminished significantly with increasing duration of diabetes. We conclude that B cell function is correlated to pancreatic enzyme secretion and that patients with insulin-treated diabetes secondary to chronic pancreatitis have a residual insulin secretion similar to that of patients with Type 1 (insulin-dependent) diabetes.

Adult↗

No response of pancreatic hormones to hypoglycemia in diabetic autonomic neuropathy.

The responses of pancreatic hormones (i.e. glucagon, pancreatic polypeptide, and somatostatin) to insulin-induced hypoglycemia were investigated in 18 insulin-dependent diabetics without residual beta-cell function and in 6 normal subjects. Nine of the diabetics had autonomic neuropathy, and 9 had no neuropathy. After hypoglycemia, no significant increase in any of the 3 pancreatic hormones was found in the diabetics with autonomic neuropathy, whereas significant increments were found in the diabetics without neuropathy and in the normal subjects. These results suggest that autonomic nervous activity is of major importance for pancreatic hormone release during hypoglycemia in man.

Adult↗