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Biomedical subjects

U Panten

Publications and source records attributed to U Panten.

At least 73 records · Page 4Linked 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

O2 consumption by isolated pancreatic islets, as measured in a microincubation system with a Clark-type electrode.

The role of B-cell respiration in fuel-induced insulin secretion has not been clarified. Therefore, a new method for the measurement of O2 uptake in islets of Langerhans was developed. An all-glass microincubation chamber was equipped with a Clark-type electrode, a stirring bar, and a special channel for loading the chamber with islets, media, and test compounds. The sensitivity of the system was sufficient for convenient determination of O2 consumption by less than 100 islets. Using DNA as reference value, the exactness of the method was scaled up considerably. Basal O2 uptake in mouse islets amounted to 5.6 +/- 0.2 nmol/h/micrograms DNA. alpha-Ketoisocaproic acid (2.5-20 mM) enhanced O2 consumption by 63-207%. The rate of O2 uptake as well as those of insulin secretion and oxidation of alpha-ketoisocaproic acid in incubated mouse islets were maximal at about 10 mM alpha-ketoisocaproic acid. 14CO2 production from U-14C-labeled alpha-ketoisocaproic acid was up to 36% lower than the corresponding increase in O2 uptake. However, the differences were partly caused by insufficient mixing of media in the oxidation studies. D-Glucose (20 mM) released more than twice the amount of insulin than 5 mM alpha-ketoisocaproic acid, although O2 uptake in the islets did not differ. The results are consistent with the view that an increase in the production of metabolic energy is necessary for recognizing insulin-releasing fuels by B-cells.

Animals↗
PubMed1981

Mechanism of 3-phenylpyruvate-induced insulin release from isolated pancreatic islets.

3-Phenylpyruvate evoked a monophasic insulin release from perifused mouse islets. L-Phenylalanine was not an insulin secretagogue and was oxidized by islets at a very low rate, suggesting that 3-phenylpyruvate does not trigger insulin release by enhancing production of reducing equivalents. Moreover, allosteric activation of glutamate dehydrogenase does not play a role in 3-phenylpyruvate-induced insulin secretion.

Amino Acids↗
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

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

Studies on the role of beta-cell metabolism in the insulinotropic effect of alpha-ketoisocaproic acid.

alpha-Ketoisocaproic acid has been shown to be a potent insulin secretagogue but the mechanism has not been elucidated. To define the role of beta-cell metabolism in the insulinotropic activity of alpha-ketoisocaproic acid the utilization of glucose and the oxidation of alpha-ketoisocaproic and isovaleric acid by incubated islets of obese hyperglycemic mice were measured. Glucose metabolism was never enhanced by alpha-ketoisocaproic acid. The same 14CO2 amounts were released from the non-secretagogue [1-14C]isovaleric acid (10 mM) or from alpha-keto[2-14C]isocaproic acid (5--20 mM). Pyruvate (20 mM) did not inhibit alpha-ketoisocaproic acid-induced insulin secretion in spite of reduction of decarboxylation of alpha-ketoisocaproic acid by more than 40%. The results indicate that stimulated insulin release in response to alpha-ketoisocaproic acid is not mediated by an indirect increase in glucose metabolism and further suggest that isovaleryl-CoA and following CoA-esters in alpha-ketoisocaproic acid degradation are not likely recognized as signals. The possibility, however, remains that enhanced intramitochondrial production of reducing equivalents elicits insulin secretion.

Animals↗
PubMed1978

Comparison of alpha-ketoisocaproic acid and glucose in rats: effects on insulin and somatostatin release and on islet cAMP content.

The insulinotropic effects of alpha-ketoisocaproic acid and glucose reveal many common characteristics in vivo and in vitro. They qualify as initiators of insulin release, their action is amplified by potentiators of insulin release, and they have a similar potency at equimolar concentrations. The dynamics of insulin release evoked by alpha-ketoisocaproic acid and glucose are similar. Epinephrine completely inhibits the insulinotropic effect of glucose and alpha-ketoisocaproic acid. Mannoheptulose exhibits a complete, immediate and reversible blockade of glucose-induced insulin release. In contrast, inhibition of alpha-ketoisocaproic acid-induced insulin release occurs after a lag period and is not reversed by removal of the inhibitor. alpha-ketoisocaproic acid, at equimolar concentrations, is several-fold more effective than glucose in elevating cAMP content in islet. alpha ketoisocaproic acid and glucose are about equally effective in stimulating somatostatin release from isolated rat pancreatic islets. This stimulation is inhibited by epinephrine. Mannoheptulose inhibits only somatostatin release induced by glucose but not by alpha-ketoisocaproic acid. It suggested that the insulinotropic characteristics of glucose and alpha-ketoisocaproic acid reveal many common features, while their mode of action appears to be different.

Animals↗
PubMed1976

Effects of D-glyceraldehyde and 3-o-methylglucose upon fluorescence of reduced pyridine nucleotides from perifused isolated pancreatic islets.

In perfused pancreatic islets, the fluorescence of reduced pyridine nucleotides was recorded continuously, D-Glyceraldehyde (5 mM) or 3-o-methylglucose (27.5 mM) never caused a net fluorescence increase. Since stepwise changes of the D-glucose concentration between 0 and 20 mM always induced a fluorescence increase, it is concluded that glucose on the one hand and glyceraldehyde or 3-o-methylglucose on the other hand cause different metabolic states in pancreatic islets.

Animals↗