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Biomedical subjects

E F Pfeiffer

Publications and source records attributed to E F Pfeiffer.

At least 253 records · Page 14Linked to original sources

Studies on the pituitary "fettstoffwechselhormon". VII. Analytical studies on two lipolytically high active peptides from hog pituitary glands.

First results of analytical studies on the highly purified lipolytic active hog pituitary fractions P-LF II C and P-LF II D are reported. Electrophoresis and end-group determinations indicate homogeneity for both peptides. The molecular weights, amino acid compositions, and the N- and C-terminal sequences of these peptides have been established and are compared with the corresponding results of other laboratories. The relation between biological activity and the structure of lipolytic active peptides is discussed.

Amino Acid Sequence↗

Attempts at perfect normalization of glucose tolerance test of severe diabetics by artificial beta cell.

The artificial beta cell is a Glucose Controlled Insulin (and dextrose) Infusion System (GCIIS) for maintaining normoglycemia in diabetic conditions and other disturbances of metabolism. The insulin and dextrose infusion rates are calculated by a microcomputer according to the static glucose concentration (proportional control) and to its rate of change (dynamic control). The algorithms controlling the computer can be adapted to the subjects' requirements. It has already been shown, that the artificial beta cell is able to maintain blood sugar values in diabetics within physiological ranges during the course of the day. In our present study we examined the response of the artificial beta cell using a 100 gm oral glucose load in severe diabetics. The first type of control algorithms applied effected a rather small initial insulin infusion following OGTT in 8 juvenile diabetics connected with the artificial beta cell. The glucose responses thus obtained were similar to latent diabetes. In contrast, when the computer was controlled by the second type of algorithms with a more responsive dynamic control and a consequently higher initial insulin infusion, in one diabetic OGTT was fully normalized, whereas an improvement was achieved in another diabetic patient. Furthermore it was shown that control algorithms must be varied individually, depending on residual beta cell function and glucose regulatory mechanisms.

Blood Glucose↗

Studies on the pituitary "fettstoffwechselhormon". VI. Preparation of two highly purified lipolytic active peptides from hog pituitary glands.

The preparation of two highly purified lipolytically active hog pituitary peptides, called P-LF II C and P-LF II D is described. The two peptides are free of other pituitary hormone activities. In isolated rat and porcine adipose tissue, both fractions are lipolytically much more active than every other lipolytic active pituitary peptide described to date. By fraction P-LF II D, the first pituitary peptide was isolated which has lipolytic activity in isolated rat adipose tissue than corticotropin, the lipolytically most active pituitary hormone known so far. On isolated porcine adipose tissue, fraction P-LF II D as well as P-LF II C showed without doubt higher activity than corticotropin.

Adipose Tissue↗

Effects of somatostatin on exocrine and endocrine pancreatic function stimulated by intestinal hormones in man.

To evaluate the action of somatostatin on exocrine and endocrine pancreatic function, synthetic somatostatin (GIF) was administered (intravenous bolus of 300 mug followed by a constant 60-minute infusion, 5 mug/min) to 17 normal subjects. The secretin-induced volume and total bicarbonate contents of the duodenal aspirate were not affected whereas the bicarbonate concentration was significantly diminished. GIF reduced decisively the pancreatic enzyme secretion stimulated by pure (99%) cholecystokinin-pancreozymin. After the GIF infusion was stopped, a significant rise in enzyme secretion was observed. The secretin-induced insulin release was almost completely suppressed. Because GIF can be extracted in large quantities from pancreas, these data suggest that somatostatin may play a physiological role in the regulation of the secretory processes of this organ. Furthermore, GIF may be a useful adjunct in the treatment of acute pancreatitis.

Bicarbonates↗

Growth hormone radiologand assay unresponsive to human prolactin.

A specific and sensitive radioligand assay for growth hormone with female rat liver plasma membranes is presented. Growth hormones of different species are able to displace labelled human growth hormone from membrane binding sites with parallel standard curves. Human prolactin V-L-S is not equal to 1 and the international human prolactin standard MRC 71/222 do not affect the assay. Human prolactin preparations with different growth hormone content displace human growth hormone tracer only to the same extent as they contain growth hormone when measured by radioimmunoassay.

Animals↗

Hypoglycemia in diabetics.

Hypoglycemia in diabetes can be divided into 1) spontaneous hypoglycemic reactions due to absolute or relative overproduction of endogenous insulin or some other blood glucose-lowering substance, as in islet cell adenoma or carcinoma, latent or protodiabetic conditions, (extrapancreatic) tumors and pituitary and/or adrenal disorders; and 2) hypoglycemia caused by exogenous, i.e. therapeutic, measures. The problem of hypoglycemia in insulin-treated diabetics is far from being solved. As revealed by continuous blood glucose monitoring, nocturnal hypoglycemic attacks frequently escape attention especially in juvenile diabetics. Circadian variations in peripheral glucose utilization, rather than changes in plasma insulin activity, are likely to be involved in this mechanism. At least, this was the conclusion drawn from studies carried out by means of a glucose-controlled insulin and glucose infusion system (GCIGIS) -or artificial pancreas-which delivers short-acting insulin and glucose on demand intravenously. Hypoglycemic reactions in patients being treated with oral anti-diabetic agents, on the other hand, should be regarded primarily as one of the side reactions intrinsic to the mechanism of action of some of these drugs, e.g. sulfonylureas, which act mainly via stimulation of secretion of endogenous insulin reserves not responding properly to postprandial blood glucose increments. In the case of glibenclamide, at least partial resensitization of the defective glucose receptor of the beta-cell also becomes operative. A higher incidence of a characteristic type of hypoglycemic reaction was observed soon after glibenclamide therapy was introduced. Better understanding of the drug and dissemination of the information about it to doctors and patients has reduced the number of hypoglycemic reactions caused by glibenclamide to the same proportions as for other sulfonylureas. Hypoglyoemia following therapeutic hypophysectomy retains its position as one of the main hazards of this heroic therapy.

Adenoma, Islet Cell↗

High-molecular IRI (big, big insulin) in islet cell adenoma.

In agreement with data previously reported (Yalow and Berson 1973), after gel filtration of acid-ethanol extracts of islet cell adenomas (performed in 3 M acetic acid) 1.4% to 1.8% of total immunoreactive insulin (IRI) eluted ahead of proinsulin. The high-molecular IRI (HM-IRI) was, however, found to be heterogenous in size and consisted of at least three components, the major one having an estimated molecular weight of about 50,000. Under certain conditions, HM-IRI was partially dissociated into proinsulin- and insulin-like components. We conclude that HM-IRI does not represent a precursor of proinsulin and insulin, but probably a self-association product of the peptides or an association of insulin and proinsulin to other proteins extracted from tumor tissue.

Adenoma↗

[Interaction between gastrointestinal hormones and endocrine regulation].

The vicinity of several hormone-producing glands as part of the anatomy of the intestinal tract and the resulting interaction has been confirmed by the discovery of hormonal factors of a specifically gastro-intestinal origin. Today we are mainly interested in the interaction between intermediary metabolism and incretory intestinal function; this is characterized by the joint action of conventional glandular hormones such as insulin and pancreatic glucagon as well as by the incretion of diffuse intestinal organs, hormones such as secretin, pancreozymin, motilin, VIP and GIP. The latter are at present subject of active research with the object of discovering their physiological significance be it as tissue hormones or as humoral agents with a "long distance" impact; their role within pathophysiology is also of interest. GIP ("gastric inhibitory peptide"), apart form acting upon the intestinal tract, also causes a marked rise in insulin production; this GIP possibly is the factor responsible for the difference in glucose tolerance following i. v. or oral administration of glucose, something that scientists have been trying to discover for a long time. We have also endeavored to investigate somatostatin. This substance was originally discovered as a hypothalamic factor with inhibitory action on growth hormone secretion; in the meantime, however, cells containing and possibly also producing somatostatin have also been detected in the intestine and particularly in the islets of Langerhans (D-cells). Since somatostatin inhibits insulin secretion and especially glucagon release as well as the exretory functions of the stomach and of the pancreas, the significance of this hormone possibly is that of a tissue hormone with inhibitory action on adjacent cells. As factor inhibiting both endocrine and exocrine secretory processes it would combine these two complexes. The possible therapeutic significance of somatostatin administration to diabetics would lie in the saving of insulin. A third sector of present-day research deals with the interaction between the calcium metabolism and the hormones involved as well as the intestine. We know that patients suffering from primary hyperparathyroidism are prone to contract stomach ulcers and pancreatitis; patients with a gastrinoma and a hyperfunction of the epithelial bodies suffer from a Zollinger-Ellison-sindrome and this again suggests association with endocrine polyadenomatosis (Wermer syndrome). The inhibitory action of the parathormone antagonist calcitonin on the exocrine functions of the intestinal tract, such as the acid secretion of the stomach and the enzyme secretion of the pancreas, have already given rise to some considerations and experiments relative to treatment. It is to be hoped that because of all the joint observations cited above there will be better intergration of research both from the aspect of gastro-enterology and endocrinology. This might hopefully elucidate some of the unresolved problems ranging from basic research to practical application.

Adolescent↗

Gastrin concentration in plasma of the neonate at birth and after the first feeding.

Plasma gastrin was determined simultaneously in 19 newborn infants and their respective mothers shortly after birth and in ten neonates before and after the first feeding. The gastrin concentrations in the umbilical vein plasma of the newborn infants were significantly higher than in the peripheral vein plasma of their mothers. The values were statistically not different from those obtained in the neonates before the first feeding. There was an increase in gastrin concentrations after the first feeding. From these results it is suggested that gastrin is produced in the neonate independently from the mother. It is already secreted after the first feeding. Experiments in rats showed that 125I-gastrin is not transported through the placenta. From these findings we assume that most likely the gastrin measured in plasma of newborn infants is of neonatal origin.

Adult↗

(Pro-) insulin biosynthesis and release of newly synthesized (pro-) insulin from isolated islets of rat pancreas in the presence of amino acids and sulphonylureas.

The influence of arginine, lysine, tolbutamide and glibenclamide on (pro-) insulin biosynthesis and release of newly synthesized (pro-) insulin was studied in isolated islets of rat pancreas. Islets were incubated with 3H-leucine and glucose in the presence and absence of the test agents. Proinsulin and insulin of islets and incubation media were separated by gel filtration on Sephadex G 50. Estimations were carried out for radioactivity and immunoreactivity for insulin. All four substances were able to enhance insulin release whereas no stimulation of leucine incorporation into (pro-) insulin was found. Arginine and tolbutamide even markedly reduced (pro-) insulin aynthesis. Conversion of proinsulin to insulin was not affected by any of the test agents. For studying the influence of the 4 substances on secretion of newly synthesized (pro-) insulin two experimental models were used: 1) Labelling of the islets in the presence of the test agents, followed by uniform stimulation with glucose alone in the presence or absence of Ca++. 2) Addition of the 4 test substances after uniform prelabelling of the islets. 1) Presence of arginine and sulfonylureas during labelling resulted in a significantly enhanced relative fractional release of newly synthesized (pro-) insulin, although the bulk of secreted hormone appeared to stem from the storage pool also under these conditions. The enhanced fractional release was persistent also during the postlabelling period when the islets had been labelled in the presence of arginine or glibenclamide. On the other hand, a decreased release of newly synthesized (pro-) insulin was obsevered during the postlabelling period in islets labelled in the presence of tolbutamide. Lysine was without significant effects in both periods. Omission of calcium ions during the postlabelling period inhibited the release of both immunoreactive and radioactive hormone. 2) When amino acids or sulphonylureas were added after prelabelling no significant changes were found in the specific radioactivity of released (pro-) insulin or in the fractional release of newly synthesized hormone. Enhanced release of fresh granules from the beta cell might explain the increased fractional release of newly synthesized (pro-)insulin when lebelling is carried out in the presence of arginine and sulphonylureas, especially glibenclamide.

Amino Acids↗