Protein kinase activities in rat pancreatic islets of Langerhans

Sugden, Mary C.; Ashcroft, S. J. H.; Sugden, Peter H.

doi:10.1042/bj1800219

Cited by 42 publications

(21 citation statements)

References 39 publications

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“…This finding correlates with our recent finding in the perfused pancreas and isolated islets of GK rats, that generation of cAMP by forskolin restores the insulin response to 16.7 mmol/l glucose and, furthermore, elicits a pronounced insulin release also at 3.3 mmol/l glucose [13]. It has been shown that cAMP induces protein phosphorylation in beta cells, especially through activation of protein kinase A [14,15]. Thus, in such a manner cAMP-induced activation of protein kinase A could interact with other proteins of importance for the exocytotic process [16].…”

Section: Discussionsupporting

confidence: 80%

Preserved initiatory and potentiatory effect of α-ketoisocaproate on insulin release in islets of glucose intolerant rats

et al. 1998

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Glucose-stimulated insulin secretion is severely impaired in the Goto-Kakizaki (GK) rat, which is an animal model of hereditary non-obese Type II (non-insulin-dependent) diabetes mellitus [1±3]. F 1 hybrids of GK and healthy Wistar rats show nearly normal fasting blood glucose concentrations but impaired glucose tolerance and decreased insulin response to glucose, in the presence of a normal pancreatic insulin content [4]. The diabetic state is thus milder in F 1 hybrid rats than in GK rats, as indicated by the intermediate glucose tolerance and insulin responses to glucose in the perfused pancreas compared with those representative of GK and control rats [4].The impaired insulin response to glucose in F 1 hybrid rats is most likely an inherited defect which is not related to intrauterine hyperglycaemia and glucose toxicity [4,5]. The mechanism behind this defect Diabetologia (1998) Summary Insulin responses to glucose and non-glucose secretagogues were studied in short-term cultured pancreatic islets and perfused pancreata of the glucose intolerant F 1 hybrid rats of spontaneously diabetic Goto-Kakizaki and control Wistar rats. After culture at 5.5 mmol/l glucose, hybrid islet responses to 11.1, 16.7 and 27.0 mmol/l glucose were between 60 and 40 % of control islet responses. A combination of 1 mmol/l isobutylmethylxanthine and 16.7 mmol/l glucose induced a pronounced insulin release, which was of similar magnitude in hybrid and control rat islets. This response was not further augmented by addition of glibenclamide and arginine. The slope of potentiation of arginine (10 mmol/l)-stimulated insulin secretion by glucose (5.5±16.7 mmol/l) was greatly impaired in hybrid islets. In contrast to glucose, a-ketoisocaproate (KIC), which is metabolized in Krebs cycle, dose-dependently stimulated insulin secretion to similar levels in hybrid and control islets, cultured at 5.5 mmol/l glucose. Also in hybrid islets depolarized by potassium chloride (30 mmol/l) and with adenosine triphosphate-sensitive K + -channels kept open by diazoxide, insulin responses to glucose were greatly impaired but intact to KIC. Furthermore, KIC potentiated normally the insulin response to arginine in hybrid islets. In the isolated perfused pancreas, KIC induced similar insulin responses in hybrid rats and control rats. The potentiating effect by 5.5 mmol/l glucose on the KIC-stimulated insulin responses was, however, greatly reduced in isolated islets and absent in the perfused pancreata of hybrid rats. Taken together, these findings suggest an intact capacity for insulin release, although the initiating and potentiating effect by glucose on insulin release are defective in the Goto-Kakizaki-hybrid rats. An abnormal beta-cell glucose metabolism proximal to the Krebs cycle is likely to account for the impairment of insulin release. [Diabetologia (1998

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Section: Discussionsupporting

confidence: 80%

Preserved initiatory and potentiatory effect of α-ketoisocaproate on insulin release in islets of glucose intolerant rats

et al. 1998

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“…Indeed, the slow and reduced exocytosis in cells perfused with solutions lacking ATP or containing 3 mM AMP-PNP is consistent with the occurrence of protein dephosphorylation in the absence of ATP. PKA catalyzes the phosphorylation of many proteins in beta cells (41), but the protein substrate responsible for the action of ATP on exocytosis remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Post-priming actions of ATP on Ca ²⁺ -dependent exocytosis in pancreatic beta cells

Takahashi

Kadowaki

Yazaki

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

153

130

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Medical Sciences. In the article "Activation of protein kinase C correlates with a cardioprotective effect of regular ethanol consumption" by Masami Miyamae, Manuel M. Rodriguez, S. Albert Camacho, Ivan Diamond, Daira Mochly-Rosen, and Vincent M. Figueredo, which appeared in number 14, July 7, 1998, of Proc. Natl. Acad. Sci. USA (95, 8262-8267), the following correction should be noted. On page 8264, an incorrect Fig. 1 was printed. The correct figure and its accompanying legend are reproduced below.Neurobiology. In the article "Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase" by Piera Pasinelli, David R. Borchelt, Megan K. Houseweart, Don W. Cleveland, and Robert H. Brown, Jr., which appeared in number 26, December 22, 1998, of Proc. Natl. Acad. Sci. USA (95, 15763-15768), the following corrections should be noted. An erroneous version of Fig. 6 was published. The lane indicated as G41D represents lumbo-sacral spinal cord extract from G85R transgenic mice. In Fig. 7a, cell viability is expressed as % of untreated cells and not as % of viability. Physiology FIG. 1. LVDP prior to 45 min of global ischemia and duringreperfusion in four groups of perfused guinea pig hearts (n ϭ 9 for each group): 1, following 8 wk 15% ethanol-derived calories (E); 2, pair-fed controls (‚); 3, following 8 wk of ethanol, before and after 10 mM chelerythrine (F); and 4, pair-fed controls, before and after chelerythrine (s). LVDP recovery is significantly greater in hearts from ethanol-treated animals (P Ͻ 0.05 at each 6-min interval). Chelerythrine abolished ethanol's protective effect on LVDP recovery. Data are presented as mean Ϯ SEM (SEM not included for group 2 but lie well within SEM of groups 3 and 4). 3330Corrections Proc. Natl. Acad. Sci. USA 96 (1999) Communicated by Erwin Neher, Max Planck Institute of Biophysical Chemistry, Goettingen, Germany, November 13, 1998 (received for review August 25, 1998 ABSTRACTThe role of cytosolic ATP in exocytosis was investigated by using amperometric measurement of insulin exocytosis in pancreatic beta cells, which were stimulated with photolysis of caged Ca 2؉ compounds. Insulin exocytosis occurred with two rates. We found that ATP hastened and augmented the exocytosis via selective enhancement of the exocytosis with the faster rate. A nonhydrolysable analog of ATP, adenosine 5-O-(3-thiotriphosphate), which blocks ATPase, was even more effective than ATP, indicating that the phosphorylation event occurred downstream of ATPdependent vesicle transportation and priming. The action of ATP was eliminated by a competitive antagonist of cAMP, and by an inhibitor of adenylate cyclase. These data characterize an ATP sensing mechanism for the Ca 2؉ -dependent exocytosis involving adenylate-cyclase, cAMP-dependent protein kinase, and, possibly, the fusion machinery itself. Thus, the fast exocytotic machinery requires both phosphorylation and Ca 2؉ for the final triggering and likely constitutes a di...

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“…The regulatory subunit possesses two cAMP binding sites (known as "A" and "B") that act cooperatively (Su et al, 1995). It is not clear which isoforms of PKA are present in human β cells: however both PKA type I and II have been isolated from DEAE-cellulose ion-exchange chromatography of rat islets (Sugden et al, 1979). Regulatory unit type RIIα has been detected by western blot in mouse islets (Kashima et al, 2001).…”

Section: Activation Of Pkamentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

577

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Protein kinase activities in rat pancreatic islets of Langerhans

Cited by 42 publications

References 39 publications

Preserved initiatory and potentiatory effect of α-ketoisocaproate on insulin release in islets of glucose intolerant rats

Preserved initiatory and potentiatory effect of α-ketoisocaproate on insulin release in islets of glucose intolerant rats

Post-priming actions of ATP on Ca ²⁺ -dependent exocytosis in pancreatic beta cells

Mechanisms of action of glucagon-like peptide 1 in the pancreas

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Protein kinase activities in rat pancreatic islets of Langerhans

Cited by 42 publications

References 39 publications

Preserved initiatory and potentiatory effect of α-ketoisocaproate on insulin release in islets of glucose intolerant rats

Preserved initiatory and potentiatory effect of α-ketoisocaproate on insulin release in islets of glucose intolerant rats

Post-priming actions of ATP on Ca 2+ -dependent exocytosis in pancreatic beta cells

Mechanisms of action of glucagon-like peptide 1 in the pancreas

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Post-priming actions of ATP on Ca ²⁺ -dependent exocytosis in pancreatic beta cells