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Biomedical subjects

K Hermansen

Publications and source records attributed to K Hermansen.

At least 127 records · Page 7Linked to original sources
PubMed1985

In vivo insulin action in type 1 (insulin-dependent) diabetic pregnant women as assessed by the insulin clamp technique.

To determine the influence of pregnancy on insulin sensitivity in patients with type 1 diabetes mellitus in more detail, a hyperinsulinemic euglycemic clamp study was performed in six pregnant type 1 diabetic women and eight nonpregnant women with type 1 diabetes mellitus. All of the pregnant women were studied three times: in early pregnancy (mean, week 13), late pregnancy (mean, week 34), and within a week after delivery. Insulin was infused in a constant rate of 1.0 mU/kg X min, which resulted in steady state serum free insulin levels (I) of 44 +/- 3 (+/- SEM), 56.6 +/- 6, and 55 +/- 8 microU/ml in the pregnant diabetic women and 52 +/- 4 microU/ml in the nonpregnant women. Mean glucose disposal (M) was 5.6 +/- 0.3 mg/kg X min early in pregnancy and 3.4 +/- 0.5 mg/kg X min late in pregnancy (P less than 0.02). However, in the early postpartum period, M was again higher (7.2 +/- 0.7 mg/kg X min; P less than 0.02) and similar to values in early pregnancy and nonpregnant diabetic women (7.2 +/- 0.6 mg/kg X min). When tissue sensitivity to insulin was expressed as the M to I ratio, similar results were obtained (nonpregnant women, early stage of gestation, and postpartum vs. late stage of gestation: 0.13 +/- 0.01, 0.13 +/- 0.01, and 0.15 +/- 0.03 mg/kg X min per microU/ml vs. 0.06 +/- 0.1 mg/kg X min per microU/ml; P less than 0.03 in all). There tended to be an inverse relationship between serum levels of human placental lactogen and the M to I ratio during pregnancy (r = -0.74; P = 0.09). However, we found no association between changes in the impairment of insulin action and serum estradiol, progesterone, or cortisol levels. In conclusion, pregnant type 1 diabetic women have insulin resistance in peripheral tissues in the late stage of gestation. Insulin sensitivity returns to values found in nonpregnant diabetic women within the first week after delivery.

Adult↗
PubMed1985

Reversal of D- and A-cell insensitivity to glucose in alloxan-diabetic dogs by treatment with the artificial beta cell (Biostator).

Insulin-deficient diabetes in man as well as in experimental diabetes is associated with islet cell insensitivity to glucose. The present study was designed to determine whether this abnormality could be counteracted either by increasing the intraislet insulin level or by normalizing the diabetic state by a glucose-controlled insulin infusion system (GCIIS: Biostator, Life Science Instruments, Elkhart, Indiana). Using the isolated, perfused pancreas of dogs with moderate, untreated alloxan diabetes of 4 days duration, we found that 5 mM arginine (N = 4) and 5 mM calcium (N = 4) stimulated D- and A-cell secretion, whereas an increment in glucose from 1.3 to 11 mM (N = 4) had no effect on islet hormone secretion. In the pancreas from untreated alloxan-diabetic dogs, acute infusion of large amounts of insulin (25 mU/ml) in vitro simultaneously with an elevation of perfusate glucose from 1.3 to 11 mM failed to restore the glucose from 1.3 to 11 mM failed to restore the glucose sensitivity. In contrast, treatment of alloxan-diabetic dogs (N = 3) by a GCIIS for 24 h revived some responsiveness of the glucagon, insulin, and somatostatin to glucose (1.3-11 mM) of the subsequently perfused pancreas. It is concluded that the insensitivity to glucose of islet cells in insulin-deficient diabetes is not ascribed to an intra-islet insulin deficiency per se but rather to an abnormal metabolic state secondary to insulin deficiency. The results also indicate that the glucose receptor dysfunction is not due to a direct lesion by the diabetogenic drug.

Animals↗
PubMed1984

Effects of cholecystokinin (CCK)-4, nonsulfated CCK-8, and sulfated CCK-8 on pancreatic somatostatin, insulin, and glucagon secretion in the dog: studies in vitro.

The effect of cholecystokinin (CCK)-4, nonsulfated CCK-8 (CCK-8), and sulfated CCK-8 (CCK-8-S) on endocrine pancreas function was investigated in the isolated perfused dog pancreas in the presence of 5.5 mM glucose. CCK-4 and CCK-8 at concentrations of 1, 10, and 100 nM dose dependently stimulated pancreatic SRIF, insulin, and glucagon release. The insulinotropic and glucagonotropic potency of CCK-8 was significantly greater than that of CCK-4, whereas the effect on SRIF secretion was similar. Furthermore, CCK-8-S and CCK-8 at concentrations of 0.1, 1, and 10 nM caused a dose-dependent increase in pancreatic A, B, and D cell secretion. The CCK-8-S was a more potent insulinotropic agent than CCK-8. It is suggested that these principal molecular CCK forms qualify for a physiological modulatory role in the endocrine pancreas.

Animals↗
PubMed1983

Enkephalins and the secretion of pancreatic somatostatin and insulin in the dog: studies in vitro.

Enkephalins are naturally occurring peptides with powerful opiate-like effects which have recently been found in nerves of the pancreas. To assess the nature and extent of the influence that opiates exert on the endocrine pancreas, we examined the effects of MET-enkephalin (MEK), leu-enkephalin, morphine, and the opiate antagonist naloxone (NAL) as well as adrenergic and cholinergic blockade on the hormone release from the isolated perfused dog pancreas. It was found that MEK (1-100 nM) dose dependently inhibited somatostatin release and stimulated insulin secretion. The effects of MEK (100 nM) were modulated by the prevailing glucose concentration. Thus, more pronounced changes in D and B cell release were obtained at high (11 mM) rather than at low (1.3 mM) glucose. Ten micromolar of morphine inhibited somatostatin and stimulated insulin secretion, effects being antagonized by NAL (10 microM). NAL (10 microM) similarly counteracted the MEK (50 nM)-induced pertubations in islet hormone secretion. NAL (10 microM) per se did not affect somatostatin or insulin secretion at 8.3 mM glucose. Infusions of either 1 microM phentolamine, 1 microM propranolol, or 1 microM atropine did not significantly alter the amount of somatostatin or insulin secretion during the infusion of 50 nM MEK. In conclusion, the results are suggestive of enkephalins reaching the islets by neural pathways and directly modifying islet hormone secretion by directly interacting with opiate receptors on the islet cells.

Animals↗
PubMed1982

Stimulatory effect of beta-hydroxybutyrate on the release of somatostatin from the isolated pancreas of normal and streptozotocin-diabetic dogs.

The present investigation was undertaken to ascertain whether the ketone body, beta-hydroxybutyrate (BOH), affects the somatostatin secretion from the isolated pancreas of normal and streptozotocin (STZ)-diabetic dogs. We found (1) that the addition of 10 mM DL-BOH to the perfusate augmented somatostatin secretion from the normal dog pancreas. The responses obtained were, however, modified by the prevailing glucose level with higher responses appearing at high (11 mM) rather than at zero glucose. The effect of BOH could not be attributed to changes in osmolarity, Na+, or H+ concentrations. (2) BOH at doses well within the physiologic and pathophysiologic range stimulated the secretion of somatostatin from the normal pancreas in a dose-dependent manner. The threshold concentration was close to 1 mM corresponding to 0.5 mM of the biologically active D form. (3) In the STZ-diabetic dogs, BOH (1-20 mM) elicits a dose-related enhancement of the pancreatic somatostatin secretion. In the two groups, identical D-cell responses were obtained at 3, 10, and 20 mM BOH. The results demonstrate that physiologic levels of BOH stimulates the release of somatostatin from pancreas of normal and STZ-diabetic dogs, thereby providing support for a physiologic influence of BOH over the secretory function of the pancreatic D-cell. The possible existence of a BOH-somatostatin feed-back mechanism operating in the diabetic organism is discussed.

3-Hydroxybutyric Acid↗
PubMed1981

Characterisation of the abnormal pancreatic D and A cell function in streptozotocin diabetic dogs: studies with D-glyceraldehyde, dihydroxyacetone, D-mannoheptulose, D-glucose, and L-arginine.

Pancreatic D and A cell function is deranged in streptozotocin diabetes. To investigate this, the effect of D-glyceraldehyde, dihydroxyacetone, D-mannoheptulose and glucose variations during arginine stimulation on the release of somatostatin and glucagon from the isolated pancreas of normal and streptozotocin diabetic dogs was studied. Concentrations of the trioses, D-glyceraldehyde (1.25 and 2.5 mmol/l) and dihydroxyacetone (11 mmol/l), which normally stimulate D cells, did not influence the release of somatostatin in the diabetic dog. However, the higher concentration of D-glyceraldehyde (5 mmol/l) and dihydroxyacetone (11 mmol/l), which normally stimulate D cells, did not influence the release of somatostatin in the diabetic dog. However, the higher concentration of D-glyceraldehyde (5 mmol/l) suppressed D cell ssecretion in the diabetic animals at 0 and 8.3 mmol/l glucose. A cell secretion was significantly suppressed at the higher glucose level in response to both 2.5 and 5 mmol/l of te triose. This inhibition may be explained by a non-specific effect induced by the high dose of this triose. The addition of 5 mmol/l mannoheptulose, which normally reduces glucose-induced somatostatin secretion and stimulates glucagon release, did not affect hormone secretion. In both the diabetic and the normal animals, arginine (5 mmol/l) stimulated somatostatin and glucagon secretion. Although arginine was able to stimulate D and A cell secretion in the diabetic dogs, it was however unable to restore the response to changes in glucose concentration between 1.4 and 8.3 mmol/l to normal. These results demonstrate that the abnormal pancreatic D and A cell function in streptozotocin diabetes is characterised by an impaired response to glucose and certain glucose metabolites and probably results from a specific defect in glucose recognition.

Animals↗
PubMed1981

Pancreatic D-cell recognition of D-glucose: studies with D-glucose, D-glyceraldehyde, dihydroxyacetone, D-mannoheptulose, D-fructose, D-galactose, and D-ribose.

To investigate how the D-cell recognizes the glucose stimulus, the hormone response to (1) glucose, (2) the trioses glyceraldehyde and dihydroxyacetone, (3) the metabolic blocker, mannoheptulose, and (4) the low- or nonmetabolized sugars galactose, fructose, or ribose were studied using the isolated dog pancreas. We found (1) a sigmoidal relationship between extracellular glucose concentrations and the somatostatin release. The threshold concentration was around 5 mM and the largest increase in somatostatin release occurs between 5 and 10 mM of glucose. (2) Glyceraldehyde at concentrations ranging between 1.25 and 5 mM stimulated the release of somatostatin, whereas the higher concentrations of 10 and 20 mM were suppressive. Dihydroxyacetone (11 mM), also initiated somatostatin release in the absence of glucose. Both of the trioses stimulated B- and inhibited A-cell secretion. (3) Mannoheptulose (5 mM) attenuated somatostatin and insulin secretion to 8.3 mM glucose, while it augmented glucagon output. In contrast, mannoheptulose (5 mM) did not affect D-, A-, or B-cell responses to glyceraldehyde (5 mM) in the absence of glucose. (4) The somatostatin, insulin, and glucagon release remained unchanged when 8.3 mM of either galactose, fructose, or ribose was added. The results suggest that the initiation of glucose-mediated D- as well as A- and B-cell responses depends on the metabolism of the sugar.

Animals↗
PubMed1980

Characterization of the inhibitory effect of somatostatin upon insulin and glucagon release in the isolated perfused canine pancreas: evidence for interaction with calcium.

Somatostatin is a potent inhibitor of insulin and glucagon release from the isolated perfused canine pancreas. The present investigation was undertaken to characterize the pancreatic effects of somatostatin by studying its ability to influence insulin and glucagon release from the same perfusion preparation in response to various well-known stimuli and modulators. Somatostatin inhibited insulin and glucagon release in all test situations chosen but one. Thus, somatostatin inhibits pancreatic hormone secretion irrespective of whether it is modulated by (1) a primary initiator of insulin release--glucose (1.3 or 8.3 mM), leucine (4.1 mM), tolbutamide (2.6 mM); (2) a potentiator of insulin release, i.e., a substance that requires the presence of glucose--arginine (1 mM); (3) substances known to increase the level of cyclic AMP (cAMP) in the islets--glucagon (2 ng/ml), cAMP (1 mM), theophylline (1 mM); (4) an autonomic agent--epinephrine (2 ng/ml), acetylcholine (10 microM); or (5) alpha and beta adrenergic antagonists--phentolamine (1 microM), propranolol (1 microM). In contrast, high Ca++ concentrations (4.8 and 8.2 mM) abolished the inhibitory action of somatostatin on both insulin and glucagon release. These findings lend support to the hypothesis that somatostatin acts at a stage of secretory processes, possibly related to Ca++ inactivation, late in the chain of events leading to hormone release.

Animals↗
PubMed1980

The significance of the Na+/K+ pump for somatostatin release.

The influence of the Na+/K+ pump on somatostatin secretion from the isolated perfused canine pancreas was investigated. The somatostatin secretion was reversibly increased in response to addition of ouabain (10(-5) mol/l) and to omission of extracellular K+, procedures which are known to cause a blockade of the Na+/K+ pump. The stimulatory effect on somatostatin release was abolished during calcium depletion. The results suggest that the operation of the Na+/K+ pump plays an important role for the somatostatin secretion. The action of the Na+/K+ pump on the secretory function of the D-cells is dependent on the presence of extracellular calcium.

Animals↗
PubMed1980

The role of sodium in somatostatin secretion: evidence for the involvement of Na+ channels in the release mechanism.

The influence of Na+ upon the secretion of somatostatin from the isolated perfused canine pancreas was studied. The Na+ channel-opening alkaloid veratridine (10 microM) was found to cause a biphasic increase in somatostatin output as a normal Ca++ concentration of 1.3 mM. The response to veratridine was inhibited 70% by the addition of 1 microM tetrodotoxin (TTX) and was totally abolished in the absence of extracellular Ca++. TTX (1 microM) reversibly inhibited (by 30%) the glucose-induced somatostatin secretion. During Ca++ depletion, the inhibitory effect of TTX was eliminated. Partial replacement of extracellular Na+ by choline (40 mM Na+ and 100 mM choline) caused a 3- to 4-fold increase in somatostatin secretion. This finding and the fact that the somatostatin response to Na+ withdrawal required the presence of extracellular Ca++ suggest that the stimulatory effect of a decrease in extracellular Na+ concentration is mediated, at least in part, by a Na+-Ca++ countertransport mechanism. The results indicate that the Na+-mediated somatostatin release is dependent upon the extracellular Ca++ concentration. It is unlikely that Na+ per se or via redistribution of the intracellularly bound Ca++ can stimulate somatostatin secretion.

Animals↗
PubMed1980

Effects of substance P and other peptides on the release of somatostatin, insulin, and glucagon in vitro.

We studied the actions of substance P, bombesin, vasoactive intestinal peptide (VIP), and the octapeptide of cholecystokinin (CCK-8-S) on the release of somatostatin, insulin, and glucagon from the isolated perfused pancreatico-duodenal canine preparation. Substance P at concentrations ranging from 0.2-5.0 nM stimulated the secretion of somatostatin, insulin, and glucagon in a dose-dependent manner. However, the responses evoked by substance P were modified by the prevailing glucose level; higher somatostatin and insulin and lower glucagon responses were obtained at the high glucose concentration of 8.3 mM rather than at the low glucose concentration of 2.8 mM. At a glucose concentration of 5.5 mM, somatostatin release was above the prestimulation level in response to 1 nM substance P (89 +/- 15%; P less than 0.01), VIP (49 +/- 7%; P less than 0.01), or CCK-8-S (99 +/- 21%; P less than 0.01); bombesin was without effect (16 +/- 14; P = NS). Insulin release was enhanced by substance P (150 +/- 45%; P less than 0.05), bombesin (162 +/- 56%; P less than 0.05), VIP (44 +/- 5%; P less than 0.01), and CCK-8-S (190 +/- 17%; P less than 0.001). Furthermore, a significant release of glucagon was evoked by 1 nM substance P (501 +/- 158%; P less than 0.05), bombesin (30 +/- 10%; P less than 0.05), VIP (43 +/- 8%; P less than 0.01), or CCK-8-S (140 +/- 19%; P less than 0.001).

Animals↗
PubMed1980

Duodenal contribution to pancreaticoduodenal vein islet hormones during stimulation of the canine pancreas with calcium.

The possible influence of the duodenum on pancreatic hormones in the pancreaticoduodenal venous affluent of the canine pancreas was studied. The magnitude and dynamics of somatostatin, glucagon, and insulin responses during stimulation with 5 mM calcium were identical whether or not the duodenal remnant was excluded from the perfusion by clamping. The results indicate that during perfusion with calcium the duodenal remnant is without any significant regulatory or contributory role on pancreatic hormone secretion from the isolated canine pancreas preparation.

Animals↗
PubMed1979

Characterisation of somatostatin release from the pancreas: the role of calcium and acetylcholine.

The effect of calcium on somatostatin secretion was investigated in the isolated, perfused canine pancreas preparation and compared with those of acetylcholine, glucose, isoproterenol and arginine. Calcium (5 mmol/l) stimulated somatostatin release in a typical biphasic response pattern being about 5 times as potent as acetylcholine (1 mumol/l), arginine (5 mmol/l), and isoproterenol (2 ng/ml) while the release of insulin and glucagon in response to calcium and the other secretagogues were of the same magnitude. Somatostatin release increased progressively when perfusate calcium was increased step-wise from 0 through 1.25 and 2.5 to 5.0 mmol/l. Calcium stimulated the secretion of somatostatin in the absence of glucose. The stimulatory effect of calcium was, however, modulated by the glucose concentration being about twice as large at 200 mg/100 ml as at 25 mg/100 ml glucose in the perfusion medium.

Acetylcholine↗
PubMed1979

Streptozotocin diabetes: a glucoreceptor dysfunction affecting D cells as well as B and A cells.

Somatostatin release from the isolated pancreas of 3 normal and 6 streptozotocin diabetic dogs has been measured in response to various stimuli to determine whether abnormalities in somatostatin release are present in the diabetic pancreas. Simultaneous measurement of glucagon secretion was also made. In the pancreas from normal dogs increases in perfusate glucose from 25 to 200 mg/100 ml induced a 2--3 fold increase in somatostatin release and a two thirds decrease in glucagon secretion. In contrast, in the diabetic pancreas glucose caused no change in the secretion of the two hormones. In the diabetic pancreas addition of insulin to the perfusate (25,000 microU/ml) for periods from 10 to 75 minutes aimed at restoring normal extracellular insulin levels in the islets failed to restore either somatostatin or glucagon secretion to normal. In contradistinction to the lack of effect of glucose, the somatostatin and glucagon responses to arginine (5 mmol/l), isoproterenol (2 ng/ml) and calcium (5 mmol/l) were normal in the diabetic pancreas. The data suggests the presence of a selective glucoreceptor abnormality of the D as well as of B and A cells in the streptozotocin diabetic dog.

Animals↗