ergoline and Diabetes-Mellitus

The present study was aimed at investigating the effect of metergoline, a powerful and long-lasting antiserotoninergic agent, on insulin responses to glucose and arginine in adult-onset diabetic subjects. The repeated administration of this agent (10 mg daily for two days plus a 4 mg dose 1 hour before the post-treatment test) or placebo did not influence acute insulin response to intravenous glucose (20 g), total insulin secretion or glucose disappearance rates. Similarly, plasma glucose and insulin levels following arginine (30 g perfused over a period of 40 min) were similar before and after metergoline treatment. These results do not support the hypothesis that an endogenous monoamine mechanism plays an important part in defective insulin secretion in human non insulin-dependent diabetes mellitus.

Topics: Adult; Arginine; Blood Glucose; Diabetes Mellitus; Ergolines; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Kinetics; Metergoline; Middle Aged

Oxidant stress secondary to dopamine metabolism has been proposed as a pathogenic factor in the development of Parkinson's disease. Biochemical abnormalities extending beyond the central nervous system have been identified in patients with this condition. Previous investigators have found abnormally elevated concentrations of the lipid peroxidation product, malondialdehyde, in the plasma and serum of patients with Parkinson's disease. We attempted to replicate these findings but controlled for other factors that could influence malondialdehyde levels. We detected no significant elevations in mean serum malondialdehyde concentrations in either levodopa-treated or untreated patients with Parkinson's disease, compared to normal controls; similarly, no elevation was found in a group of patients with dementia of Alzheimer's type. On the other hand, a group of subjects with diabetes mellitus but no neurodegenerative disease had significantly elevated mean serum malondialdehyde levels, consistent with previous studies of diabetic patients. Autoxidation is one of the two major routes by which dopamine and dopa metabolism may generate oxygen free radicals. We analyzed the autoxidation product of dopa, 5-S-cysteinyl-dopa, in the plasma of these same groups of patients with neurodegenerative disease and normal controls; no significant differences were identified. Serum concentrations of two other antioxidant substances, alpha-tocopherol and uric acid, were also statistically similar in these groups. In conclusion, analysis of several blood products relevant to oxidant stress, including malondialdehyde, 5-S-cysteinyl-dopa, alpha-tocopherol, and uric acid, failed to distinguish patients with Parkinson's disease or dementia of Alzheimer's type from controls.

Topics: Aged; Alzheimer Disease; Antiparkinson Agents; Brain; Cabergoline; Carbidopa; Diabetes Mellitus; Ergolines; Female; Free Radicals; Humans; Levodopa; Lipid Peroxidation; Male; Malondialdehyde; Oxidative Stress; Parkinson Disease; Selegiline; Vitamin E

Topics: Animals; Aortic Coarctation; Auscultation; Bacteriological Techniques; Cholecystography; Diabetes Mellitus; Ephedrine; Epinephrine; Ergolines; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Hypophysectomy; Penicillins; Poliomyelitis; Positive-Pressure Respiration; Staining and Labeling; Sulfapyridine; Tuberculosis, Pulmonary

Specific 125I-labeled prolactin binding was measured in membrane particles prepared from R3230AC mammary carcinoma and liver of tumor-bearing Fischer rats after either prolactin, estrogen, or lergotrile mesylate treatment, or after the induction of diabetes by streptozotocin. Hormone binding to tumors was decreased by treatment with prolactin (0.5 or 1 mg/day) or estradiol valerate (7.5 mg/kg/week). In contrast, prolactin treatment did not affect prolactin binding to liver membrane particles, but estradiol valerate treatment resulted in a four-fold increase in prolactin binding to this tissue. Lergotrile mesylate, which lowers plasma prolactin levels, did not affect tumor growth or prolactin binding to either tumor or liver. Prolactin binding to both tumor and liver was significantly reduced in diabetic rats, suggesting that insulin may play an important role in controlling tissue sensitivity to prolactin. Specific binding of 125I-labeled prolactin to enzymatically dissociated cells from R3230AC tumors was demonstrated in vitro. The binding capacity of the cells was found to be of the same order of magnitude as the binding capacity in membrane preparations when appropriate corrections were applied for yields of cells and membranes. R3230AC tumor, which is responsive to prolactin appears therefore to be a useful model system for further study aimed at elucidation of growth and metabolic response to the hormone prolactin in breast cancer.. Specific iodine-125-labeled prolactin binding was measured in membrane particles prepared from R3230AC mammary carcinoma and liver of tumor-bearing Fischer rats after either prolactin, estrogen, or lergotrile mesylate treatment, or after the induction of diabetes by streptozotocin. Hormone binding to tumors was decreased by treatment with prolactin (.5 or 1 mg/day) or estradiol valerate (7.5 mg/kg/week). In contrast, prolactin treatment was without affect on prolactin binding to liver membrane particles, but estradiol valerate treatment resulted in a 4-fold increase in prolactin binding to this tissue. Lergotrile mesylate, which lowers plasma prolactin levels, had no affect on tumor growth or prolactin binding to either tumor or liver. Prolactin binding to both tumor and liver was significantly reduced in diabetic rats, suggesting that insulin may play an important role in controlling tissue sensitivity to prolactin. Specific binding of iodine-labeled prolactin to enzymatically dissociated cells from R3230AC tumors was demonstrated in vitro. The binding capacity of the cells was found to be of the same order of magnitude as the binding capacity in membrane preparations when appropriate corrections were applied for yields of cells and membranes. R3230AC tumor, which is responsive to prolactin, appears therefore to be a useful model system for further study aimed at elucidation of growth and metabolic response to the hormone prolactin in breast cancer.

Topics: Acetonitriles; Animals; Binding Sites; Diabetes Mellitus; Ergolines; Estradiol; Female; Insulin; Liver; Mammary Neoplasms, Experimental; Membranes; Prolactin; Rats; Receptors, Cell Surface; Streptozocin

In twenty-two patients with active acromegaly who were untreated or unsuccessfully operated or irradiated (mean growth hormone (GH) values greater than 4 ng/ml) the following investigations were performed: routine laboratory tests, tomography of pituitary fossa, oral glucose tolerance tests, TRH and other pituitary function tests and GH profiles over 5-10 h before and during bromocriptine treatment with daily doses between 7.5 and 50 mg. In seventeen patients GH was suppressed to less than 50% by bromocriptine, in thirteen of them it was normalized on at least one occasion. A TRH induced GH release was observed in all but two responders to bromocriptine before therapy. This effect of TRH was not blunted during treatment with bromocriptine and also in the two patients with negative tests before therapy a significant GH increase was observed. In no non-responder to bromocriptine was a significant increase of GH after TRH observed. One patient showed a secondary resistance to bromocriptine during a period of treatment with griseofulvin. In the remaining sixteen patients the GH suppression has been consistent for between 3 and 22 months. A single dose of pimozide abolished the bromocriptine effect on GH totally in one patient; in others a slight or no significant effect was observed. Tissue swelling and sweating decreased in all bromocriptine responders and glucose tolerance improved in five patients. In four diabetic patients a partial or full remission of diabetes occurred. Apart from postural hypotension after the first administration in two patients no other severe side effects have been observed. Sella size and the other pituitary functions did not change during the time of the study. It seems that a high percentage of acromegalics may be successfully treated with bromocriptine.

Topics: Acromegaly; Adult; Aged; Bromocriptine; Diabetes Mellitus; Ergolines; Female; Growth Hormone; Humans; Male; Middle Aged; Pimozide; Thyrotropin-Releasing Hormone

Topics: Adult; Aged; Arginine; Clofibrate; Diabetes Mellitus; Ergolines; Female; Glucose Tolerance Test; Growth Hormone; Humans; Male; Metergoline; Middle Aged; Obesity; Sex Factors; Triglycerides

The estrogen-binding capacity of mammary tumors induced by 7,12-dimethylbenz(a)anthracene was measured in lesions from animals after the ovariectomy, deprival of insulin (diabetes), or treatment with lergotrile mesylate to inhibit prolactin secretion. The average estrogen-binding capacity was 30 fmoles/mg cytosol protein in growing or static carcinomas from intact (control) animals. A significant reduction in estrogen-binding capacity was observed in regressing but not static mammary tumors from ovariectomized animals. In regressing and static tumors from diabetic rats, estrogen-binding capacity was significantly lower than in lesions from intact animals; this effect was not seen in growing tumors from diabetic rats. Tumors that were growing or static in lergotrile-treated animals showed reduced capacity to bind labeled estradiol. The effects of duration of hormone treatment or time of tissue storage on estrogen-binding capacity were examined and did not appear to be correlated with the decreased binding in tumors from treated animals. The results suggest that hormones capable of producing altered neoplastic growth may influence the level of estrogen receptors.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetonitriles; Animals; Castration; Diabetes Mellitus; Ergolines; Estradiol; Estrogens; Female; Insulin; Mammary Neoplasms, Experimental; Prolactin; Rats; Streptozocin; Time Factors

Oral administration of 1.0 or 2.5 mg bromocriptine (CB 154: 2-brom-alpha-ergocryptine) in nine of twelve patients with active acromegaly resulted in a reduction of growth hormone level by 80-90% over 8-10 hours. During treatment for 2-9 months with daily doses of 4.0 to 10.0 mg bromocriptine, there was a sustained reduction of growth hormone levels in these patients. At the same time soft-tissue swellings and tendency towards sweating decreased. In two patients with diabetes mellitus the blood sugar profile improved and in one of them the insulin dose could be markedly reduced. The rise in growth hormone levels after TRH administration also occurred during bromocriptine treatment. In those patients in whom growth hormone levels failed to react to either acute or chronic administration of bromocriptine no rise followed TRH administration. It is possible that in these patients there is a hypophyseal adenoma without hypothalamic control. On gradually increasing dosage bromocriptine was tolerated without side effects.

Topics: Acromegaly; Administration, Oral; Blood Glucose; Bromocriptine; Diabetes Complications; Diabetes Mellitus; Ergolines; Female; Growth Hormone; Humans; Male; Sweating; Time Factors

The effect of metergoline on insulin secretion has been evaluated in normal subjects and in patients with chemical diabetes. The repeated administration of metergoline, 2 mg at four-hour intervals to give a total of 24 mg, has enhanced insulin secretion in response to i.v. glucose in normal subjects but not in chemical diabetics. No changes in blood glucose pattern were observed. Under similar conditions, metergoline administration caused a slight but significant decrease in arginine-induced insulin release, both in normal subjects and in chemical diabetics. These results support the concept of a serotoninergic control of insulin secretion and suggest that serotonin exerts different effects on insulin release according to the different stimuli.

Topics: Arginine; Blood Glucose; Diabetes Mellitus; Ergolines; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Metergoline; Serotonin Antagonists