Search PubMed⌕ Search

Biomedical subjects

M Lorenzi

Publications and source records attributed to M Lorenzi.

At least 91 records · Page 5Linked to original sources
PubMed1980

Increased growth hormone response to dopamine infusion in insulin-dependent diabetic subjects: indication of possible blood-brain barrier abnormality.

To test the hypothesis that cerebral capillaries, which share the embroyologic and morphologic characteristics of retinal capillaries, might have the same abnormal permeability in diabetic patients, we investigated the growth hormone response to a small amount of peripherally administered dopamine (1.5 microgram/kg.min). Consistent with the known exclusion of systemic dopamine from brain parenchyma, no rise was observed in 12 normal subjects. In 10 of 12 juvenile-onset, insulin-dependent diabetic patients, however, a substantial growth hormone rise occurred (peak value, 19.2 +/- 3.0 ng/ml [mean +/- SE]). Comparision of metabolic and cardiovascular responses to the infusion in both groups did not suggest that higher circulating levels of dopamine had been achieved in the diabetics. Other growth hormone stimuli (apomorphine in decreasing amounts, glucagon, and graded physical exercise) failed to indicate that hypothalamic hypersensitivity could account for the consistent rise. We postulate that an abnormal permeability of the blood-brain barrier in the diabetic patients permitted exposure of the hypothalamic structures regulating growth hormone secretion to a greater fraction of the infused dopamine.

Adult↗
PubMed1979

Feedback-controlled dextrose infusion during surgical management of insulinomas.

Through the use of a feedback-controlled dextrose infusion system, we obtained continuous monitoring of the blood glucose level in a patient undergoing surgery for multiple pancreatic beta-cell tumors. In addition, this device infused dextrose at variable rates to maintain a predetermined euglycemic level of 90 mg/dl. Before locating the source of excessive insulin production, the maximum dextrose infusion rate of 400 mg/min was required; but after extirpation of multiple insulinomas, the dextrose-infusion rate declined whereas the blood glucose level rose above the preselected level. These results emphasize the usefulness of a monitoring and infusion system not only in protecting the patient from the hazard of hypoglycemia under anesthesia but also as an aid in determining whether all insulin-secreting tumors have been removed.

Adenoma, Islet Cell↗
PubMed1979

Diabetic management by insulin infusion during major surgery.

In five insulin-requiring, uremic diabetic patients undergoing renal transplantation, we infused insulin intravenously at a low rate to maintain plasma glucose levels between 100 and 200 mg/100 ml. In those patients receiving 100 mg or more of prednisone per day and 5 per cent dextrose solution, the hourly infusion rate was determined from tthe following equation: insulin (U) = plasma glucose value divided by 100. When prednisone was not given or when the patient was thin, the ratio became: plasma glucose value divided by 150. Results were compared with those of nineteen similar transplant patients treated with conventional subcutaneous insulin therapy during surgery, and significantly better glucose control was achieved with the low dosage, intravenous infusion.

Adult↗
PubMed1979

Dopamine during alpha- or beta-adrenergic blockade in man. Hormonal, metabolic, and cardiovascular effects.

We studied the contribution of alpha- and beta-adrenergic receptor activation to the cardiovascular, metabolic, and hormonal effects of dopamine. At a concentration of 1.5 mug/kg.min, the infusion of dopamine in 12 normal volunteers was associated with a transient but significant rise in pulse rate, which was prevented by propranolol. Venous plasma glucose did not change throughout the experiments, and a mild increase in plasma free fatty acid levels observed during the administration of dopamine alone was antagonized by propranolol. In contrast, neither the beta-adrenergic blocker, propranolol, nor the alpha-adrenergic blocker, phentolamine, was effective in inhibiting the dopamine-induced rise in plasma glucagon (from 82+/-9 to 128+/-14 pg/ml; P < 0.005) and serum insulin (from 7.5+/-1 to 13+/-1.5 muU/ml; P < 0.005) or its suppression of plasma prolactin (from 8.5+/-1 to 5.2+/-0.8 ng/ml; P < 0.001). Although serum growth hormone levels did not change during the infusion of dopamine alone, an obvious rise occurred in three subjects during the combined infusion of propranolol and dopamine. Whereas some metabolic and cardiovascular effects of dopamine are mediated through adrenergic mechanisms, these observations indicate that this is not the case for the effects of this catecholamine on glucagon, insulin, and prolactin secretion, and thus provide further support for the theory of a specific dopaminergic sensitivity of these hormonal systems in man.

Adrenergic alpha-Antagonists↗
PubMed1979

Phentolamine and the action of somatostatin in man.

The inhibition by somatostatin (SRIF) of basal and arginine-stimulated glucagon, insulin, and glucose levels was compared with that obtained when SRIF was preceded by alpha-adrenergic blockade with phentolamine. No noteworthy differences were observed, except that the characteristic rebound of insulin upon discontinuation of SRIF was significantly lower with phentolamine (P less than 0.01). These results indicate that inhibition of basal and arginine-stimulated glucagon and insulin secretion by SRIF in man is not mediated through activation by alpha-adrenergic receptors.

Adult↗
PubMed1978

[Surgical treatment of carcinoma of the pancreas].

Personal experience acquired in the use of radical and palliative techniques in the treatment of 18 cases of carcinoma of the pancreas and 1 of carcinoma of the ampulla hepatopancreatica is reported. The results show that duodenocephalo-pancreasectomy is a sound procedure, particularly in the absence of lymph node invasion. Operative mortality is low if the surgeon is experienced. In the even of serious and prolonged cholostasis, the operation can be preceded by a biliary shunt. According to the Authors there are not yet valid reasons as to the survival to prefer total pancreasectomy instead the partial pancreasectomy because of the high mortality of the former. Early diagnosis and the recognition of precancerous conditions still represent determining factors as far as operability and hence survival are concerned. The efficacy of chemotherapy is uncertain at present.

Aged↗
PubMed1977

Plasma glucagon suppression by phenformin in man.

In an attempt to elucidate the mechanism of action of phenformin, eleven juvenile-onset, insulin-requiring diabetic subjects underwent four different treatment regimens during standard breakfast tests. These four treatments were: control (no insulin or phenformin); insulin alone (15 U regular insulin administered subcutaneously one-half hour before breakfast); phenformin alone (50 mg of the timed-release capsule given twice daily for three days before the study and two and one-half hours before breakfast on the day of study); and phenformin plus insulin (in the amounts and at the times stated above). Phenformin was found to decrease postprandial hyperglycaemia significantly when compared with control values, and its addition to insulin further decreased the postprandial glucose rise below that found with insulin alone (p less than 0.005). These effects were associated with a reduction in early (30-min) postprandial hyperglucagonaemia (p less than 0.05). Triglyceride levels, gastrin secretion, growth hormone levels, and increments of alpha-amino nitrogen were not affected by phenformin. Thls, suppression of postprandial hyperglucagonaemia may be an additional mechanism in the reduction of postprandial hyperglycaemia after phenformin.

Adult↗
PubMed1977

Cushing's disease: growth hormone response to hypoglycemia after correction of hypercortisolism.

Growth hormone responses to insulin-induced hypoglycemia were studied in 17 patients with inactive Cushing's disease. A normal GH rise was found in 9 of 9 patients without evidence of progressive pituitary tumor after bilateral adrenalectomy and 3 of 4 patients after correction of hypercortisolism by transsphenoidal removal of pituitary microadenomas. In contrast, 3 of 4 patients with Nelson's syndrome had impaired GH responsiveness to hypoglycemia. These results show that GH responsiveness is normal in the majority of patients with inactive Cushing's disease and do not support the concept of a primary hypothalamic or central nervous system abnormality of GH regulation in Cushing's disease.

Adrenalectomy↗
PubMed1977

Differential effects of L-dopa and apomorphine on glucagon secretion in man: evidence against central dopaminergic stimulation of glucagon.

In 6 normal subjects, L-dopa (500 mg PO) and apomorphine (0.6 mg sc) increased circulating growth hormone and suppressed prolactin levels in a parallel and quantitatively similar fashion, but only L-dopa induced a rise in plasma glucagon, glucose, and insulin levels. The failure of apomorphine to affect glucagon secretion, despite a substantial effect on growth hormone and prolactin, was also observed in insulin-dependent diabetics known to exhibit A-cell hyperresponsiveness to various stimuli. In view of the highly dissimilar molecular and pharmacologic characteristics of L-dopa and apomorphine, these data do not exclude a local dopaminergic effect of L-dopa at the pancreatic level, but strongly militate against a central dopaminergic pathway for glucagon stimulation.

Adult↗
PubMed1977

Plasma cyclic nucleotide levels in juvenile-onset diabetes.

In patients with juvenile-onset diabetes, plasma concentrations of 3',5'-adenosine cyclic monophosphate (cAMP) were significantly lower than those of norman subjects [16 +/- 4 and 24 +/- 7 pmol per milliliter (p less than 0.025), respectively] as determined in this laboratory; whereas there were essentially no differences in plasma levels of 3',5'-guanosine cyclic monophosphate (cGMP). Because cAMP inhibits cell growth and cGMP stimulates it, these findings may represent an important factor in the atherosclerotic and obliterative angiopathies of diabetic individuals. We observed that cyclic nucleotide values were the same whether or not the subjects were receiving insulin. Those given insulin plus enough glucose to maintain hyperglycemia revealed modest elevations in cyclic nucleotide levels. Thus, the ratio of cAMP to cGMP, abnormally low in juvenile-onset diabetes, is relatively independent of short-term variations in plasma levels of either glucose of insulin.

Adult↗
PubMed1977

The effect of chronic oral antidiabetic therapy on insulin and glucagon responses to a meal.

Nineteen maturity-onset diabetic patients receiving oral hypoglycemic therapy in a university diabetes clinic completed a study to assess the efficacy of the oral agents and to determine their effects on pancreatic islet hormone secretion. All patients were receiving sulfonylureas, and seven were also receiving phenformin. The subjects were studied as outpatients in the clinic setting on four different occasions with collections of a baseline blood sample before a standard breakfast and a second sampling two hours postprandially, twice while on their prescribed medication and twice after having been withdrawn from the medication. The values obtained during the two studies on the two studies off medications were reproducible for each subject. Analysis of the results by paired differences revealed that mean 24-hour urine glucose values deteriorated significantly (p less than 0.005) after oral antidiabetic therapy was withdrawn; similarly, mean plasma glucose values, both at baseline and two hours postprandially, rose significantly (p less than 0.001) when subjects were off medication. Baseline serum insulin values were not changed, but postprandial levels were significantly higher on oral agents (p less than 0.005). Plasma immunoreactive glucagon was significantly lower both at baseline (p less than 0.02) and postprandially (p less than 0.005) when the subjects were on their antidiabetic medications. During the trial off medication, 16 patients became symptomatic, with three of these developing symptoms severe enough to require hospitalization. It is apparent from this study that oral hypoglycemic medications can play a role in controlling symptoms in maturity-onset diabetic patients and that the beneficial effect of these agents on hyperglycemia may, in part, be explained by their stimulation of endogenous insulin secretion and partial suppression of endogenous glucagon.

Acetohexamide↗
PubMed1976

Role of glucagon in human diabetic ketoacidosis: studies using somatostatin.

The present studies demonstrate that endogenous glucagon is hyperglycaemic, lipolytic and ketogenic in man, and that insulin deficiency is necessary, but is in itself not sufficient, to cause fulminant diabetic ketoacidosis. Furthermore, continuous elevation of endogenous glucagon secretion appears to be necessary for the maintenance and continued development of the characteristic metabolic consequences of insulin lack.

Adult↗
PubMed1976

Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin.

To study the individual effects of glucagon and growth hormone on human carbohydrate and lipid metabolism, endogenous secretion of both hormones was simultaneously suppressed with somatostatin and physiologic circulating levels of one or the other hormone were reproduced by exogenous infusion. The interaction of these hormones with insulin was evaluated by performing these studies in juvenile-onset, insulin-deficient diabetic subjects both during infusion of insulin and after its withdrawal. Infusion of glucagon (1 ng/kg-min) during suppression of its endogenous secretion with somatostatin produced circulating hormone levels of approximately 200 pg/ml. When glucagon was infused along with insulin, plasma glucose levels rose from 94 +/- 8 to 126 +/- 12 mg/100 ml over 1 h (P less than 0.01); growth hormone, beta-hydroxy-butyrate, alanine, FFA, and glycerol levels did not change. When insulin was withdrawn, plasma glucose, beta-hydroxybutyrate, FFA, and glycerol all rose to higher levels (P less than 0.01) than those observed under similar conditions when somatostatin alone had been infused to suppress glucagon secretion. Thus, under appropriate conditions, physiologic levels of glucagon can stimulate lipolysis and cause hyperketonemia and hyperglycemia in man; insulin antagonizes the lipolytic and ketogenic effects of glucagon more effectively than the hyperglycemic effect. Infusion of growth hormone (1 mug/kg-h) during suppression of its endogenous secretion with somastostatin produced circulating hormone levels of approximately 6 ng/ml. When growth hormone was administered along with insulin, no effects were observed. After insulin was withdrawn, plasma beta-hydroxybutyrate, glycerol, and FFA all rose to higher levels (P less than 0.01) than those observed during infusion of somatostatin alone when growth hormone secretion was suppressed; no difference in plasma glucose, alanine, and glucagon levels was evident. Thus, under appropriate conditions, physiologic levels of growth hormone can augment lipolysis and ketonemia in man, but these actions are ordinarily not apparent in the presence of physiologic levels of insulin.

Adult↗
PubMed1976

Comparison of the suppressive effects of elevated plasma glucose and free fatty acid levels on glucagon secretion in normal and insulin-dependent diabetic subjects. Evidence for selective alpha-cell insensitivity to glucose in diabetes mellitus.

To examine whether abnormal pancreatic alpha-cell function found in human diabetes mellitus may represent a selective insensitivity to glucose, plasma glucagon responses to hyperglycemia and elevation of plasma free fatty acid levels (both known suppressors of glucagon secretion) were compared in juvenile-onset, insulin-requiring diabetic subjects, and in normal nondiabetic subjects. In the latter, both elevation of plasma free fatty acid levels induced by heparin administration of hyperglycemia produced by intravenous infusion of glucose resulted in a comparable 30--40% suppression of circulating glucagon levels (P less than 0.01). In the diabetic subjects, glucagon suppression by hyperglycemia (less than 20%) was less than that occurring in normal subjects (P less than 0.01), even when accompanied by infusion of supraphysiologic amounts of insulin. However, suppression of glucagon levels by elevation of plasma free fatty acids in the diabetic group was similar to that found in normal subjects and of comparable magnitude to that due to hyperglycemia in the normal subjects. These results thus demonstrate a selective impairment of the diabetic alpha-cell response to glucose and provide further evidence for the presence of an abnormal alpha-cell glucoreceptor in human diabetes mellitus.

Adult↗