Biomedical subjects
Publications and source records attributed to H Vierhapper.
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To evaluate the relative role of "diabetogenic" hormones as insulin antagonists in severe derangements of diabetic control, glucagon, cortisol, growth hormone and adrenaline were administered by continuous intravenous infusion, separately and in combination, to ketosis-prone insulin-dependent diabetics (n = 11). The amount of insulin required for the assimilation of a 50 g glucose load during the various hormone infusions was determined by means of an automated glucose-controlled insulin infusion system and used as an index of insulin effectiveness. Raising plasma hormone concentrations acutely into the range seen in severe diabetic states (glucagon 517 +/- 70 pg/ml; cortisol 32 +/- 3 micrograms/dl; growth hormone 14 +/- 3 ng/ml) did not alter significantly blood glucose profile and insulin requirement (control 11.3 +/- 1.1 U; glucagon 11.6 +/- 2.0 U; cortisol 11.1 +/- 0.4 U; growth hormone 12.9 +/- 1.4 U), except for adrenaline (plasma level 550 +/- 192 pg/ml), which caused a marked rise in blood glucose levels and a threefold increase in insulin demand (31.1 +/- 3.7 U). Combined infusion of all hormones did not potentiate significantly the latter effect (38.3 +/- 4.7 U). The effectiveness of metabolic control by insulin was assessed by a marked decrease in plasma nonesterified free fatty acids and ketone bodies upon its administration after glucose ingestion in all groups studied. It is concluded that from the hormones investigated within this study adrenaline exerts the strongest diabetogenic action during its short term administration followed by that of growth hormone. Whereas it may well be that over-insulinization of the patients by the glucose controlled insulin infusion system has overcome and disguised the smaller diabetogenic effects of cortisol and glucagon.
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To elucidate the mechanism by which somatostatin lowers blood glucose concentration and insulin requirement following carbohydrate ingestion in insulin dependent diabetic patients (IDDM; n = 6), the amount of insulin required for the assimilation of a 50 g glucose load was determined by means of an automated glucose-controlled insulin infusion system with and without concomitant somatostatin infusion. During the 3 hour period following glucose loading plasma concentrations of glucagon and growth hormone were diminished by somatostatin, as were the rise in blood glucose and insulin requirement (4.0 +/- 1.2 U) when compared with the control study (11.3 +/- 1.5 U; p less than 0.01). With cessation of somatostatin blood glucose levels and insulin requirement rose during the following 2 hour observation period (7.5 +/- 1.2 U) but remained basal during the control study (0.7 +/- 0.6 U; p less than 0.0005). Thus the integrated amounts of insulin required for glucose hormone were temporarily suppressed by somatostatin. It is concluded that the diminished insulin requirement and delayed rise in blood glucose during somatostatin administration after an oral glucose load is not due to its "antidiabetic" action by suppressing glucagon and growth hormone release. Our findings favour inhibition of intestinal carbohydrate absorption as the determining cause for the "antidiabetic" action of somatostatin.
The effect of indomethacin (75 mg/day for 3 days) on the response to i.v. angiotensin II was investigated in eight healthy, sodium-repleted, male subjects. Indomethacin reduced the release of aldosterone during the i.v. administration of angiotensin II (5, 10 and 20 ng kg-1 min-1), whereas the pressor response to angiotensin II and to succinamyl1-val5-phenylglycineacetate8-angiotensin II, an agonistic angiotensin II-analogue, was increased. Plasma renin concentration was reduced following treatment with indomethacin. These data confirm the modulatory influence of endogenous prostaglandins upon the vasoconstrictor effect of angiotensin II and could suggest a direct interference of prostaglandins with the secretion of aldosterone.
To study the influence of different blood glucose (BG) concentrations on the release of pituitary hormones, the effect of the simultaneous iv administration of LRH (200 micrograms), TRH (400 micrograms), and arginine (30 g/30 min) upon the serum concentrations of LH, FSH, TSH, PRL, and GH was determined in six male insulin-dependent diabetics. BG concentration was clamped by feedback control and an automated glucose-controlled insulin infusion system at euglycemic (BG 4-5 mmol/liter) or hyperglycemic (BG, 14-18 mmol/liter) levels. Increments in serum concentrations of LH, FSH, TSH, and PRL were similar in the euglycemic and hyperglycemic steady states, whereas the GH response to arginine was suppressed during the hyperglycemic clamp (P less than 0.01). Omission of exogenous insulin during hyperglycemia did not modify the observed hormonal responses. Thus, the release of LH, FSH, TSH, and PRL in response to adequate acute stimuli at the pituitary level is not modulated by hyperglycemia in insulin-dependent diabetes, while arginine-induced GH release is suppressed. Since the effect of arginine on GH is most likely mediated by an action on the hypothalamus, the data suggest that elevated glucose concentrations may exert their modulatory influence on GH secretion at the hypothalamic rather than at the pituitary level.
The effect of ACTH on serum concentrations of LH and FSH was studied in six healthy women in the follicular phase of the menstrual cycle, in six patients (five men, one woman) with adrenocortical insufficiency. In healthy women the i.v. administration of synthetic 1-24 ACTH (0.25 mg) induced a fall in serum concentrations of LH from 11.1 +/- 1.2 (S.D.) to 7.8 +/- 0.6 i.u./l (P less than 0.005) after 30 min and to 8.2 +/- 0.7 i.u./l after 60 min. Upon continuous infusion of 1-24 ACTH (0.25 mg i.v., t = 480 min) LH fell to 6.7 +/- 0.9 i.u./l (P less than 0.005) in healthy women and to 6.1 +/- 3.7 i.u./l (basal, 8.7 +/- 3.9 i.u./l) in healthy men. In patients with adrenocortical insufficiency serum concentrations of LH were unchanged by 1-24 ACTH. Serum concentrations of FSH were not altered by 1-24 ACTH in any of the three groups. It is suggested that the effect of ACTh on LH secretion is healthy women is mediated by the acute rise of endogenous cortisol concentrations.
To evaluate the possible alterations in thyroxine metabolism in patients with Crohn's disease (C.D.), the serum concentrations of thyroxine (T4), triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), and thyroxine binding globulin (TBG) were determined in 23 patients with C.D. and in 25 healthy controls. While concentrations of T4 and rT3 in patients with C.D. were similar to those seen in healthy controls, serum T3 was lower in patients with C.D. (0.93 +/- 0.4 ng/ml) than in controls (1.20 +/- 0.3 ng/ml, p less than 0.005). TBG concentrations were elevated in two patients with C.D., and below normal in two others. However, the group mean of TBG concentrations in patients with C.D. (23.7 +/- 6.9 micrograms/ml) was similar to that of healthy controls (21.9 +/- 3.6 micrograms/ml, p greater than 0.05). Changes in peripheral deiodination of thyroxine, enhanced in some cases by treatment with glucocorticoids and/or increased turnover of T3 may be the cause of the decreased concentration of T3 in some patients with Crohn's disease.
A female patient presented with severe hypokalemia and muscle weakness following chronic abuse of laxatives (Folia Sennae). Parenteral substitution of potassium resulted in complete normalisation of the clinical signs and of the pathologically elevated serum concentrations of CPK, LDH and GOT. The importance of laxatives as a possible cause of severe hypokalaemic conditions is underlined by this case report.
This study reports on the influence of indomethacin upon the renin--angiotensin system in three patients with Bartter's syndrome. An analogue of angiotensin II with weak agonistic properties (succinamyl1-val5-phenylglycine-acetate8-angiotensin II) induced a fall of blood pressure and a rise of plasma renin concentration but no change in plasma aldosterone. Pretreatment with indomethacin (75 mg/day) reversed the hypotensive effect of the analogue of angiotensin II and abolished the increase of plasma renin concentration. It is concluded that elevated levels of endogenous angiotensin II are of major importance for the maintenance of blood pressure in patients with Bartter's syndrome. The inhibition of the synthesis of prostaglandins reversed some, though not all, of the metabolic abnormalities in this syndrome.
The arginine-induced release of insulin, glucagon, GH, and PRL was studied in eight normal male volunteers. Pretreatment with indomethacin (150 mg for 3 days) failed to modify the effect of arginine on the release of these hormones. As both indomethacin and acetylsalicylic acid are potent inhibitors of the endogenous prostaglandin synthesis, these results indicate that the effect of acetylsalicylic acid on insulin and glucagon secretion, as described by others, seems to be unrelated to the suppression of endogenous prostaglandin synthesis.
Healthy male subjects of various age groups respond to the administration of D-Ser(TBU)6-EA10-LH-RH, an analogue of LH-RH substituted in positions 6 and 10, by a prolonged and increased release of LH and FSH. Increased serum concentrations of LH and FSH were observed 20 minutes after intravenous administration of the compound. Maximum concentrations of LH and FSH were seen after 60, and 60 to 240 minutes, respectively. Serum concentrations of both gonadotropins remained elevanted for up to 8 hours after the administration of 10 microgram of the LH-RH analogue. A dose response relationship was observed with regard to the serum concentrations of LH and FSH over the range of 1.25 to 5.0 microgram of the LH-RH analogue. The administration of 10 or 20 microgram of the compound, however, did not cause a further rise in plasma FSH, although the release of LH was further enhanced.
The response of LH and FSH upon the administration of D-Ser-(TBU)6-EA10-LH-RH, an analogue of luteinizing hormone-releasing hormone (LH-RH) with prolonged action was evaluated in 6 male patients with increased serum-concentrations of estradiol (E2) due to chronic liver disease. When compared to healthy, male controls (n = 7) basal levels of LH and FSH as well as the secretory response of both gonadotrophins upon the administration of the LH-RH-analogue were larger in patients with chronic liver disease although the qualitative pattern of response was identical with that observed in healthy males. It is concluded that elevated serum-concentrations of E2 in patients with chronic liver disease do not induce qualitative changes in the secretory response of gonadotrophins following the administration of D-Ser-(TBU)6-EA-10-LH-RH.
The antihypertensive effect of 80 mg/day of the newly synthesized beta-blocker 1-tert. butylamino-3-(2-cyclo-pentylphenoxy)-2-propanol-sulfate (penbutolol, Hoe 893d) was studied in patients (n = 36) suffering from primary hypertension in comparison to the effect of 750 mg alpha-methyldopa/day. It was demonstrated that the therapeutic effect of both drugs is identical. Furthermore it was shown that the antihypertensive effect of penbutolol under an uncontrolled diet is unrelated to the patient's basal plasma-renin concentration.
Ala1-lys17-ACTH(1-17)-4-amino-n-butylamide (ACTH1-17), a synthetic analogue of ACTH with shortened amino acid sequence exerts a corticotropic action of at least 8 hours duration in healthy male subjects after either intravenous or intramuscular administration. After intranasal administration of the compound an increased production of cortisol was observed only for three hours. The prolonged action of this new analogue of ACTH following intramuscular administration suggests that it may be of value for therapeutic purposes.
D-Ser-(TBU)3-EA10-LH-RH, an analogue of luteinizing hormone-releasing hormone (LH-RH) with prolonged action evokes in normal male and female subjects a qualitatively different secretory pattern of LH, as peak levels are reached between 30 and 60 min in males and between 120 and 240 min in females. Females with increased production of adrenal androgens due to congenital adrenal hyperplasia (off substitution therapy; N=8), idiopathic hirsutism (N=1) and adrenocortical carcinoma (N=2) present upon the administration of the LH-RH-analogue with a secretory pattern of LH and FSH which is qualitatively identical with that of normal female subjects, whereas the response of LH in these patients differs from that seen in normal males. Pre-treatment with dexamethasone did not induce any qualitative changes in the secretory response of LH and FSH upon the LH-RH-analogue in patients with increased endogenous production of adrenal androgens. A larger pool and/or a more pronounced de novosynthesis of LH, which apparently is not altered by increased levels of adrenal andorgens, may be the cause of the more pronounced and prolonged increase of LH in female subjects following the administration of the LH-RH-analogue.
D-Ser(TBU)6-EA10-LH-RH, an analogue of LH-RH with prolonged and increased effect upon the release of LH and FSH, induces in normal male subjects a secretory response of LH and FSH, which is qualitatively different from that seen in normal females. Female patients with increased plasma-concentration of testosterone due to congenital adrenal hyperplasia or adrenal neoplasm present upon the LH-RH-analogue with a secretory response of LH and FSH which is similar to that observed in normal female subjects. It is concluded that elevated plasma-adrogens fail to induce a masculine pattern of gonadotropin-secretion in patients with a genetically female determination of the hypothalamo-pituitary-gonadal system.
Succinamyl-arg-val-tyr-val-his-pro-phenylglycine acetate (succinamyl1-val5-phenylglycine acetate3-A II), an analogue of angiotensin II, has a pressor effect upon patients suffering from primary and secondary hypertension regardless of prevailing plasma renin concentration. It stimulates the release of aldosterone, whereas plasma renin concentration is not influenced. It is concluded, that this new analogue is, as far as its effect upon blood pressure and release of aldosterone in man is concerned, an agonist of angiotensin II.