Role of protein kinase C and Ca2+ in glucose-induced sensitization/desensitization of insulin secretion

The role of protein kinase C and Ca²⁺ in glucose-induced sensitization/desensitization of insulin secretion was studied. A 22–24h exposure of mouse pancreatic islets to glucose (16.7 mmol/l) in TCM 199 culture medium, with 0.26 mmol/l or 1.26 mmol/l Ca²⁺, reduced total islet protein kinase C activity to approx. 85% and 60% of control values, respectively. At 0.26 mmol/l Ca²⁺ in TCM 199 medium, exposure to glucose (16.7 mmol/l) led to a potentiation of both phase 1 and phase 2 of glucose-induced insulin secretion, and caused a shift in the dose-response curve with 10 mmol/l and 16.7 mmol/l glucose exhibiting equipotent effects in stimulation of insulin secretion. In glucose-sensitized islets, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (0.16 μmol/l) did not further potentiate induction of secretion by 10 mmol/l or 16.7 mmol/l glucose. At 3.3 mmol/l glucose, however, phorbol ester-induced secretion was augmented, and was characterized by a faster onset of secretion in glucose-sensitized islets relative to control islets. In contrast, a partial reduction in arachidonic acid (100 μmol/l)-induced insulin release was observed in glucose-sensitized islets in the absence of extracellular Ca²⁺. Increasing the Ca²⁺ concentration to 1.26 mmol/l in TCM 199 during the 22–24h exposure to glucose (16.8 mmol/l) led to inhibition of phase 1 and abolition of phase 2 of glucose (10 mmol/l, 16.7 mmol/l)-induced insulin secretion. In addition, this treatment abolished phorbol ester-induced and arachidonic acid-induced insulin secretion at 3.3 mmol/l glucose. Altogether, these data suggest that sensitization of insulin secretion is caused by a preferential down-regulation of the inhibitory effects of protein kinase C, leading to an increased first phase, and an increased coupling of glucose to the stimulatory effects of protein kinase C during the second phase of glucose-induced insulin secretion. Desensitization of insulin secretion appears to be a consequence of sustained Ca²⁺ influx, inducing extensive down-regulation of protein kinase C and also causing deleterious effects on islet cell function in protein kinase C-deprived islets.     

Role of protein kinase C and Ca2+ in glucose-induced sensitization/desensitization of insulin secretion.

The role of protein kinase C and Ca2+ in glucose-induced sensitization/desensitization of insulin secretion was studied. A 22-24 h exposure of mouse pancreatic islets to glucose (16.7 mmol/l) in TCM 199 culture medium, with 0.26 mmol/l or 1.26 mmol/l Ca2+, reduced total islet protein kinase C activity to approx. 85% and 60% of control values, respectively. At 0.26 mmol/l Ca2+ in TCM 199 medium, exposure to glucose (16.7 mmol/l) led to a potentiation of both phase 1 and phase 2 of glucose-induced insulin secretion, and caused a shift in the dose-response curve with 10 mmol/l and 16.7 mmol/l glucose exhibiting equipotent effects in stimulation of insulin secretion. In glucose-sensitized islets, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (0.16 mumol/l) did not further potentiate induction of secretion by 10 mmol/l or 16.7 mmol/l glucose. At 3.3 mmol/l glucose, however, phorbol ester-induced secretion was augmented, and was characterized by a faster onset of secretion in glucose-sensitized islets relative to control islets. In contrast, a partial reduction in arachidonic acid (100 mumol/l)-induced insulin release was observed in glucose-sensitized islets in the absence of extracellular Ca2+. Increasing the Ca2+ concentration to 1.26 mmol/l in TCM 199 during the 22-24 h exposure to glucose (16.7 mmol/l) led to inhibition of phase 1 and abolition of phase 2 of glucose (10 mmol/l, 16.7 mmol/l)-induced insulin secretion. In addition, this treatment abolished phorbol ester-induced and arachidonic acid-induced insulin secretion at 3.3 mmol/l glucose. Altogether, these data suggest that sensitization of insulin secretion is caused by a preferential down-regulation of the inhibitory effects of protein kinase C, leading to an increased first phase, and an increased coupling of glucose to the stimulatory effects of protein kinase C during the second phase of glucose-induced insulin secretion. Desensitization of insulin secretion appears to be a consequence of sustained Ca2+ influx, inducing extensive down-regulation of protein kinase C and also causing deleterious effects on islet cell function in protein kinase C-deprived islets.     

红叶石楠(Photinia X Fraseri)愈伤组织诱导研究

利用红叶石楠叶片和茎段作为外植体进行愈伤组织试验,研究了TDZ和AgNO_3及其他植物生长调节刑对红叶石楠愈伤组织诱导的影响效果.结果表明:TDZ和AgNO_3对红叶石楠愈伤组织诱导具有一定的促进作用,但需NAA配合.方能形成愈伤组织.本试验中,培养基1/2MS+AgNO_32.5 m/l+TDZ0.5 mg/l+NAA2.Omg/l对叶片有较好诱导效果,1/2MS+AgNO_32.5 mg/l+TDZ0.5 mg/l+NAA1.0 mg/l对茎段有较好诱导效果.此外,1.5 mg/l的TDZ与0.5 mg/l的2,4-D配比有较好诱导效果.光培养条件下,叶片的诱导率高于茎段;在暗培养下,茎段的诱导率高于叶片.     

Reaction of pyridoxal-5′-phosphate with γ-carboxyglutamic acid

Summary Pyridoxal-5-phosphate (PLP) reacts with -carboxyglutamic acid (Gla) to form a stable complex absorbing at 325 nm. It is suggested that a condensation occurs in which the formyl group of PLP reacts with the -amino group and the carbon atom of Gla to give a pyrrolidine derivative.     

Metabolism in Porifera XII. Further informations on the biosynthesis of 3β-hydroxymethyl-A-nor-steranes in the spongeAxinella verrucosa

Summary Direct incorporation and cold trap experiments suggest that cholest-4-en-3-one is an intermediate in the conversion of cholesterol into 3-hydroxymethyl-A-nor-cholestane in the marine spongeAxinella verrucosa. Cholest-4-en-3-one is further transformed by the sponge into cholest-4-en-3-ol, 5-cholestan-3-one and 5-cholestan-3-ol; these compounds arise from side reactions, which are not part of the major metabolic route leading to 3-hydroxymethyl-A-norsteranes.     

Metabolism of 3β-hydroxycholest-5-en-26-oic acid in hamsters

Summary Metabolism of 26-hydroxycholesterol to 3-hydroxychol-5-en-24-oic acid and other C24-bile acids has been expected to occur by way of 3-hydroxycholest-5-en-26-oic acid in studies in vitro. 3-Hydroxycholest-5-en-26-oic acid was infused intravenously into bile fistula hamsters and the following C24-bile acids were identified: 3-hydroxychol-5-en-24-oic acid, lithocholic acid, chenodeoxycholic acid, and a small amount of cholic acid.     

G-band patterns as chromosomal markers,and the interpretation of chromosomal evolution in wild sheep (Ovis)

- . Ovis musimon (2n=54) O. orientalis (2n=54) - - -O. canadensis mexicana (2n=54) O. musimon x O. canadensis ₁₂ - . ₂ 27 . - .

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Supported by National Science Foundation Grant no. GB 32114X and the Sprague Foundation. We thank Dr. T. C. Hsu for assistance in making the chromosome preparations and for advice and encouragement. The Trustees of the Rachelwood Wildlife Research Preserve generously allowed the biopsy of specimens of their custody. Mr.Arthur Popham kindly provided the specimens from Iran while Dr.R. M. Robinson obtained biopsies from the desert sheep.     

Studies on rII region of T2L phage

rII T2L , rII T4B. rII T2L rII T4B. T2L rII T4B.     

The tonically acting pulmonary receptors innervated by C fibres

. , , , , . (, ) . . .     

Some functional characteristics of the electroreceptors (the ampullae of lorenzini) of elasmobranchs

. . , ( I) , ( )- .     

Mutual replaceability of amide and ester groups in biologically active peptides and depsipeptides

, .     

Responses of resistance and capacitance vessels at various frequency electrical stimulation of sympathetic nerves

Conclusion (1) The maximal reactions of cerebral resistance vessels arise at the stimulation frequency of 30 cps, the maximal reactions of capacitance vessels at the frequency of 10 cps. (2) Reactions of resistance vessels in the pulmonary lobe increase in the range of stimulation frequencies from 11–50 cps, maximal reactions of pulmonary capacitance vessels are observed at the frequency of 30–40 cps. (3) Reactions of resistance vessels situated below the abdominal aorta bifurcation increase progressively in the range of frequencies from 6–50 cps, the magnitude of capacitance vessel reaction reaching its maximum value at 20 cps.

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30 /, — 10 /. 50 /. 30–40 /, 20 /.

     

The effect of chloramphenicol analogs on protein biosynthesis in a cell-freeEscherichia coli B system

a aaa a aa aa a a E. coli aa, a aa aa a , a a aa - a .

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Laboratory of Biological Investigations.

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Laboratory for Chemistry of Antibiotics.     

DNA synthesis and mitoses in atrial myocytes of rats with aortal stenosis

, . 2- , 1,60 ±0,59% , 0,96 ± 0,44% — . ë . , ³- .     

X-ray research for polycrystals. The formation geometry of instrumental width of the diffractional line at the investigation of the polycrystals in the translucent X-rays

: , , , - , ().     

Relationship between A-type and C-type particles in Ehrlich ascites tumor cells

Summary Intracisternal and intracytoplasmic A-type particles were discovered in Ehrlich ascites tumor cells. In addition, mature and immature C-type particles were also seen in the intercellular space. It is believed that A particles may represent a precursor or a formative stage of the C particles.Acknowledgment. The author is grateful to Professor F. P. Lisowski for his advice and helpful criticisms and to Mr Y. S. Tong for his expert technical assistance. This project was supported by a grant from the Hong Kong University Research Grants Committee.     

Mass spectrometric determination of the amino acid sequence in arginine-containing peptides

aa, a-a a- a aa - aa a -a .     

A historical review of the problem of mitogenetic radiation

Summary The miracle of caryokinesis was the starting point that stimulated Alexander G. Gurwitsch to carry out his famous mitogenetic experiments in 1923. The results obtained confirmed his hypothesis of a weak radiation from cells, which is able to trigger the growth of other cells. Extensive experimental work within the first two decades after this discovery indicated that the problem of mitogenetic radiations is generally related to the biological significance of UV-radiation. Both energetic and informational aspects have to be considered, namely radiation effective in activating molecules, and that involved in arranging them into larger units.The molecular organization of biological structures is evidently governed by nonequilibrium conditions needing the uptake or emission of radiation. These concepts of A. G. Gurwitsch can be linked with modern approaches based on hypotheses of coherence in biology, synergetics and dissipative structures. However, the question of causal interrelationships between this part of non-equilibrium radiation and biological matter on different levels of evolution has to be solved now.     

A new synthetic method of coumestan derivatives

Zusammenfassung Die Synthese von 7-Hydroxy-5,6-dimethoxybenzofurano[3,2:3,4]coumarin aus 7,2-Dihydroxy-oder 7-Benzyloxy-2-hydroxy-4,5-dimethoxyisoflavon wird beschrieben.     

Methylation of canine cardiac myosin in culture

Summary N, N, N, trimethyllysine and an unidentified methylated amino acid which co-electrophoresed and cochromatographed with the hydrolysis product of S-adenosyl-L-methionine, occur in fetal canine cardiac myosin and are isotopically labeled in vitro with S-adenosyl-L-(methyl³H) methionine between the 10th and the 12th day of culture.