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Biomedical subjects

S Lenzen

Publications and source records attributed to S Lenzen.

At least 109 records · Page 6Linked to original sources
PubMed1982

Signal function of metabolism of neutral amino acids and 2-keto acids for initiation of insulin secretion.

2-Ketocaproate and 2-ketoisocaproate were equally potent insulin secretagogues. The insulin secretory potency of L-leucine was less than half of that of the keto acids and L-norleucine did not induce any insulin release by isolated islets and by the perfused pancreas from ob/ob mice. Rates of decarboxylation of 2-keto-[1-14C]isocaproate and of 2-keto-[1-14C]caproate were equally high. The finding is consistent with the view that enhanced production of reducing equivalents is necessary for initiation of insulin release. The rates of decarboxylation and transamination of L-[1-14C]leucine by isolated pancreatic islets were several times higher than the rates observed with L-[1-14C]norleucine. Thus, the high activity of the pancreatic islet branched-chain amino acid aminotransferase may be important for the recognition of L-leucine as an insulin secretagogue by pancreatic B-cells.

Animals↗
PubMed1982

Inhibition of insulin secretion by L-thyroxine and D-thyroxine treatment in rats under the influence of drugs affecting the adrenergic nervous system.

Both L-thyroxine and D-thyroxine induced an inhibition of glucose-induced insulin secretion with comparable time- and dose-dependent characteristics. L-thyroxine was ten times more potent than D-thyroxine. While L-thyroxine and a ten times higher dose of D-thyroxine had a similar potency in inducing hyperthermia and hypocholesterolaemia, hyperglycaemia in response to D-thyroxine was less pronounced than in response to L-thyroxine. This difference may be explained by a greater depletion of liver glycogen stores and consequently more limited capacity for provision of glucose for the circulation. The results support the view that the differences between L-thyroxine and D-thyroxine are quantitative. Adrenergic contribution to L-thyroxine- and D-thyroxine-induced inhibition of insulin secretion by rat pancreas is apparently of minor importance. Treatment of the rats with propranolol as well as with reserpine or 6-hydroxydopamine did not alleviate L-thyroxine- or D-thyroxine-induced inhibition of insulin secretion by rat pancreas.

Animals↗
PubMed1981

Quantification of cells in islets of Langerhans using DNA determination.

DNA content seems to be an ideal reference parameter for data on secretory function or metabolism of pancreatic islets. The approved fluorometric DNA assay with diaminobenzoic acid (DABA) of Kissane and Robins comprises repeated ethanol extractions of the tissue for removal of lipids from which some DABA-reactive aldehydes may originate. In the present study it is demonstrated that only negligible amounts of DABA-positive material are extractable from islets of Langerhans. Furthermore, it is shown that various substances used in experiments on the endocrine pancreas do not interfere with the DABA-DNA reaction. A modification of the original DABA procedure which does not include ethanol extractions and which is thus more simple and accurate is described for application to pancreatic islets in the absence as well as in the presence of incubation medium. A close linear correlation between islet dry weight and islet DNA content is demonstrated. Islets from rats, normal mice, and ob/ob mice contain 38.3-39.2 ng DNA per microgram dry weight.

Aminobenzoates↗
PubMed1980

2-oxocarboxylic acids and function of pancreatic islets in obese-hyperglycaemic mice. Insulin secretion in relation to 45Ca uptake and metabolism.

The effects of aliphatic 2-oxocarboxylic acids, at concentrations of up to 40mm, on the function of pancreatic islets from ob/ob (obese-hyperglycaemic) mice were investigated. 1. 2-Oxopentanoate, dl-3-methyl-2-oxopentanoate, 4-methyl-2-oxopentanoate and 2-oxohexanoate all induced insulin release by isolated incubated islets and a biphasic insulin-secretory pattern in perfused mouse pancreas. The last two substances were similar in potency to glucose. Pyruvate, 2-oxobutyrate, 3-methyl-2-oxobutyrate and 2-oxo-octanoate did not induce insulin release significantly. 2. 2-Oxocarboxylic acids with significant insulin-secretory potency also induced significant (45)Ca uptake by isolated incubated islets. 3. The rates of decarboxylation of [1-(14)C]pyruvate, 3-methyl-2-oxo[1-(14)C]butyrate and 4-methyl-2-oxo[1-(14)C]pentanoate were twice as high as the rates of oxidation of the corresponding U-(14)C-labelled compounds. However, whereas the rates of metabolism of labelled pyruvate and 3-methyl-2-oxobutyrate steadily increased over the concentration range 1-40mm, those of labelled 4-methyl-2-oxopentanoate and d-[U-(14)C]glucose levelled off at concentrations above 10mm. 4. Omission of (40)CaCl(2) from the incubation medium reduced the rate of oxidation of the insulin secretagogue [U-(14)C]4-methyl-2-oxopentanoate, but left that of the non-(insulin secretagogue) [U-(14)C]3-methyl-2-oxobutyrate unaffected. 5. Only glucose, and not pyruvate, 3-methyl-2-oxobutyrate and 4-methyl-2-oxopentanoate, significantly inhibited oxidation of endogenous fatty acids. 6. It is suggested that stimulus-secretion coupling and the resulting exocytosis of insulin in pancreatic beta-cells may modulate both fuel oxidation and (45)Ca uptake.

Animals↗
PubMed1980

Calcium ultracytochemistry in pancreatic B-cells.

Ultracytochemical studies in B-cells using the pyroantimonate technique in combination with x-ray microanalysis demonstrated calcium deposits in association with structures of functional importance. In a series of experiments precipitate distribution has been shown to depend on the functional state of the B-cell. Increased calcium precipitation during stimulation of insulin secretion occurred at the cell membranes, in the ground plasma and the halos of the secretory granules. If these data bear functional relevance and are not only concomitant effects of the activated secretory apparatus on pyroantimonate precipitation, they may point to a direct involvement of calcium in some early steps of exocytosis and in granule transport mechanisms.

Animals↗
PubMed1980

Changes of function and metabolism of the pancreatic B-cell caused by amino acids and related compounds.

Evidence is presented that, to explain the insulin releasing capacity of L-leucine, b-BCH or alpha-ketoisocaproate (KIC), the following alternatives must be considered: 1. Interaction of the unchanged molecules with specific B-cell membrane receptors triggers insulin release. Stimulation of metabolism is a consequence of these events. 2. Primary enhancement of intramitochondrial hydrogen production triggers insulin secretion which could modulate metabolism. 3. Combination of mechanism 1 and 2: a) Additive effects of 1 and 2. b) Potentiation of 1 by 2. c) Potentiation of 2 by 1. 4. Different control of first phase or second phase of insulin release by 1, 2, or 3.

Amino Acids↗
PubMed1979

Insulin secretion by isolated perfused rat and mouse pancreas.

A method for isolation and perfusion of a pancreas preparation consisting of pancreas, stomach, proximal duodenum, and spleen is described. Basic characteristics of regulation of insulin secretion from the perfused pancreas isolated from rats, albino mice, obese mice (ob/ob), and black mice were identical. Viability and stability of the pancreas preparation during perfusion were maintained as documented by measurements of oxygen consumption of the pancreas preparation, perfusion pressure, and pH of the perfusion medium. The insulin-secretory capacity of the pancreas of different animal species was compared. Insulin secretion by the perfused rat and obese (ob/ob) mouse pancreas was much more potent than that by the pancreas of lean albino and lean black mice. D-Glucose-induced insulin secretion from the pancreas was decreased after fasting of the animals and was dependent on glucose concentration and presence of calcium in the perfusion medium. D-Glyceraldehyde, tolbutamide, D-mannose, dihydroxyacetone, L-leucine, and L-arginine also induced insulin secretion from the pancreas. D-Fructose, D-galactose, L-glucose, 3-O-methyl-D-glucose, N-acetylglucosamine, D-xylose, D,L-glyceric acid, pyruvate, L-lactate, and theophylline did not provoke insulin secretion.

Animals↗
PubMed1978

Dose-response studies on the inhibitory effect of thyroid hormones on insulin secretion in the rat.

Dose-response studies have been performed to investigate the effect of thyroid hormones on insulin secretion from the rat pancreas with special reference to the time course of the hormone effect, doses of triiodothyronine (T3) and thyroxine (T4), and glucose concentration in the perfusion medium. The prominent effect of thyroid hormones was the inhibition of the late phase of glucose-induced insulin secretion. As the late phase comprises at least 98%-99% of insulin released from the pancreas during a 60-min stimulation period with glucose, 60-min cumulative values were calculated. Both T3 and T4 inhibited insulin secretion and induced concomitant inhibitory effects on plasma cholesterol levels, a parameter of experimental hyperthyroidism. The correlation demonstrates that inhibition of glucose-induced insulin secretion from the pancreas is a specific effect of thyroid hormones. The inhibitory effect of T3 was five times greater than the inhibitory effect of T4. An excess of thyroid hormones induced hyperthyroidism, with its well-known increased incidence of diabetes.

Animals↗
PubMed1978

Further studies on the relationship between insulin release and lanthanum-nondisplaceable 45Ca2+ uptake by pancreatic islets: effects of fructose and starvation.

Relationships between the release of insulin and the incorporation of 45Ca2+ into a lanthanum-nondisplaceable (intracellular) pool were studied in islets microdissected from the pancreatic glands of non-inbred ob/ob mice. In comparison with D-glucose, D-fructose was slowly oxidized and had only marginal effects on insulin release. However, fructose was as effective as glucose in stimulating the lanthanum-nondisplaceable 45Ca2+ uptake. The 45Ca2+ uptake was dose-dependent on the concentration of fructose in the range 0-20 mM; the same dose-dependence was obtained with glucose. Fasting the mice for 3 days caused a total block of the insulin secretory response to 20 mM glucose, but it produced an enhancement of the glucose-induced 45Ca2+ uptake. Both the inhibition of insulin release and the enhancement of 45Ca2+ uptake were counteracted by pretreating the isolated islets with 20-40 mM D-glucose; pretreatment with L-glucose or fructose could not counteract the effects of fasting. Although some functional relationship may exist between the lanthanum-nondisplaceable uptake of 45Ca2+ and the insulin secretory apparatus, it is concluded that the uptake of Ca2+ is not simply the result of stimulated insulin release.

Animals↗
PubMed1978

Insulin secretion and the morphological and metabolic characteristics of pancreatic islets of hyperthyroid ob/ob mice.

Thyroxine treatment induced experimental hyperthyroidism in ob/ob mice, inhibited glucose-induced insulin secretion from the isolated perfused ob/ob mouse pancreas, and reduced total pancreas insulin content. In contrast, glucose-induced insulin release from incubated pancreatic islets and insulin content of pancreatic islets from ob/ob mice isolated by freehand microdissection were not reduced after thyroxine treatment when expressed per microgram dry islet. Histological examination of the ob/ob mouse pancreas revealed islets without degenerative lesions of islet cells. Granularity of beta cells was well preserved. The average number of pancreatic islets was unchanged. However, the beta cell area was significantly decreased in relation to the total pancreatic parenchyma after thyroxine treatment. This implies that insulin release and content per pancreatic islet was half of that of the controls. ATP content of islets was slightly reduced. Glucose oxidation and glucose utilization by islets from treated mice were slightly increased. Thyroxine treatment of the animals did not abolish the stimulation of 45Ca2+ uptake by glucose, but it did suppress the potentiating effect of fasting on the stimulatory effect of glucose on 45Ca2+ uptake. The metabolic characteristics of islets from experimentally hyperthyroid mice are those of all hyperthyroid tissues. The results provide no evidence for the view that the effects of thyroxine treatment may be due to disturbed metabolic function or energy deprivation of pancreatic islets. Inhibition of insulin secretion from the pancreas after thyroxine administration is apparently due to a reduction in pancreas insulin content and a diminished pancreatic islet volume. Reduced pancreatic islet volume represents most probably a reduction of individual islet cell volume.

Adenosine Triphosphate↗
PubMed1977

Effects of various modifiers of insulin release on the lanthanum-nondisplaceable 45Ca2+ uptake by isolated pancreatic islets.

The uptake of 45Ca2+ by a lanthanum-non-displaceable pool in pancreatic islets was studied; Raising the extracellular D-glucose concentration from 3 to 20 mM stimulated the 45Ca2+ uptake in hand-dissected islets of ob/bo-mice as well as in collagenase-isolated islets of ob/ob or normal mice. The effect was dose-dependent in the range of 0-20 mM D-glucose and was seen throughout a wide range of extracellular calcium concentrations (16 mumol-2.56 mmol of Ca2+ added per litre of medium). The 45Ca2+ uptake was also enhanced by other known insulin secretagogues (D-mannose, L-leucine, tolbutamide) and was uninfluenced by compounds lacking insulin-releasing capacity (3-O-methyl-D-glucose, L-glucose, D-galactose, D-leucine). The stimulatory effect of D-glucose was blocked by inhibitors of glucose-induced insulin release (D-mannoheptulose, diazoxide, L-adrenaline). The results support the view that the lanthanum-nondisplaceable calcium pool is related to the insulin-releasing mechanism, although the exact nature of this relationship is still unclear.

Animals↗
PubMed1976

Inhibition of insulin and glucagon release from the perfused rat pancreas by cyproheptadine (Periactinol, Nuran).

The tricyclic compound cyproheptadine (Periactinol, Nuran) inhibited glucose-induced insulin release from the perfused rat pancreas. Tolbutamide-stimulated insulin release was significantly reduced in the presence and completely suppressed in the absence of a substimulatory glucose concentration (5 mM). Arginine produced a slow rise of insulin release, which was completely abolished by cyproheptadine. Furthermore the biphasic glucagon release due to the stimulus was inhibited. Oxidation of 14C-glucose in isolated islets was unaltered in the presence of cyproheptadine, and pyruvate added to the perfusion medium failed to reverse the inhibitory effect on glucose induced insulin release, indicating that impaired glucose metabolism is not responsible for the inhibition. In addition, the inhibition remained unchanged when phentolamine was present, suggesting that the effect is not mediated by inhibitory adrenergic alpha receptors. Theophylline, in contrast, partly overcame the inhibition. When the calcium concentration of the medium was enhanced, the inhibitory effect of cyproheptadine was still visible, although the relative inhibition had become smaller. The results suggest that cyproheptadine blocks insulin release by affecting a fundamental step of the stimulus-secretion coupling common to peptide hormones. A participation of a calcium-antagonizing effect in the inhibition is discussed.

Animals↗
PubMed1976

The inhibition of insulin secretion from the perfused rat pancreas after thyroxine treatment.

Thyroxine treatment did not significantly affect the immediate insulin secretory response of the perfused rat pancreas, but it inhibited the late phase of D-glucose-induced insulin secretion. Thyroxine treatment did not inhibit D-glyceraldehyde-, D-mannose-, and tolbutamide-induced insulin release from the perfused pancreas. An increase in the D-glucose concentration of the perfusion medium as well as feeding of the rats did not restore insulin secretion after thyroxine treatment. The inhibition of D-glucose-induced insulin release in response to thyroxine treatment was reversed after addition of either D-glyceraldehyde, dihydroxyacetone, DL-glyceric acid, pyruvate, or alpha-ketobutyrate to the perfusion medium. Tolbutamide, L-glucose, D-fructose, D-mannose, L-lactate, and propionic acid were not able to overcome the inhibition of D-glucose-induced insulin secretion. Except for alpha-ketobutyrate all substances which were effective in reversing the inhibition of D-glucose-induced insulin release were glycolytic intermediates. Comparing the glycolytic alpha-ketoacid pyruvate and the non-glycolytic ketoacid alpha-ketobutyrate, the only part common to both substances was the ketoacid moiety. It is concluded from these findings that the ketoacid moiety of the alpha-ketoacids plays an important role in reversing the effect of thyroxine on D-glucose-induced insulin release.

Animals↗
PubMed1976

Thyroid function and insulin secretion from the perfused pancreas in the rat.

The influence of thyroid function on the kinetics of glucose-induced insulin secretion from the isolated perfused rat pancreas has been studied. L-Thyroxine (L-T4) administration did not modify the immediate insulin secretory response of the perfused pancreas to glucose. L-Triiodothyronine (L-T3) treatment as well as propylthiouracil (PTU) treatment decreased the immediate insulin secretory response of the pancreas slightly. Only thyroidectomy (Tx) reduced the immediate secretory response of the pancreas significantly. L-T4 and L-T3 treatment inhibited the late phase of glucose-induced insulin secretion from the isolated perfused rat pancreas, whereas TX and PTU treatment resulted in increased insulin secretion. D-Thyroxine (D-T4) did not affect glucose-induced insulin release from the pancreas. Concomitantly, several parameters indicative of thyroid function were determined in these animals. When changes in body weight, rectal temperature, plasma glucose, plasma cholesterol, and plasma butanol-extractable iodine (BEI) in these rats were compared with the insulin secretory responses, it was evident that experimental hyperthyroidism results in decreased insulin release, whereas experimental hypothyroidism induces increased insulin secretion from the pancreas. The transitions from hypothyroid to euthyroid to hyperthyroid states are accompanied by a steady decrease in glucose-induced insulin release from the rat pancreas. Inhibition of glucose-induced insulin secretion from the pancreas is therefore a specific effect of thyroid hormones.

Animals↗
PubMed1976

Inhibition o'f insulin release by cyproheptadine: effects on 3',5'-cyclic-AMP-content and 45Ca-accumulation of incubated mouse islets.

Cyproheptadine (1, 10 and 100 muM) significantly reduced insulin release from isolated mouse islets in response to glucose. In contrast, 1 mM cyproheptadine induced a large release of insulin into the incubation medium probably due to islet cell damage, since the islets had lost a considerable amount of their protein content. 3',5'-cyclic-AMP-levels of the islets were not significantly affected by 10 muM cyproheptadine in the presence as well as in the absence of theophylline (10 mM). As the inhibitory effect of cyproheptadine on insulin release was correlated with reduced accumulation of calcium-45, the agent may inhibit insulin release by interfering with the calcium handling of the beta-cell.

Animals↗
PubMed1976

The effect of hydrocortisone treatment and adrenalectomy on insulin and glucagon secretion from the perfused rat pancreas.

Hydrocortisone treatment increased blood glucose and plasma insulin levels in adrenalectomized rats. Insulin secretion during the immediate secretory response as well as the late phase of glucose-induced insulin release from the perfused pancreas from adrenalectomized rats was three times higher after hydrocortisone treatment. Glucose inhibited glucagon secretion from the perfused pancreas of adrenalectomized rats after hydrocortisone treatment but not from the pancreas of untreated animals. The immediate insulin secretory response to tolbutamide was increased by hydrocortisone treatment whereas tolbutamide did not affect glucagon release from the perfused pancreas of adrenalectomized hydrocortisone treated rats or control animals.

Adrenal Glands↗