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- Hellman, Bo, 1930-, et al.
(författare)
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Glucose generates coincident insulin and somatostatin pulses and anti-synchronous glucagon pulses from human pancreatic islets
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 150:12, s. 5334-5340
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Tidskriftsartikel (refereegranskat)abstract
- The kinetics of insulin, glucagon and somatostatin release was studied in human pancreatic islets. Batches of 10-15 islets were perifused and the hormones measured with RIA in 30-sec fractions. Increase of glucose from 3 to 20 mM resulted in a brief pulse of glucagon coinciding with suppression of basal insulin and somatostatin release. There was a subsequent drop of glucagon release concomitant with the appearance of a pronounced pulse of insulin and a slightly delayed pulse of somatostatin. Continued exposure to 20 mM glucose generated pulsatile release of the three hormones with 7- to 8-min periods accounting for 60-70% of the secreted amounts. Glucose caused pronounced stimulation of average insulin and somatostatin release. However, the nadirs between the glucagon pulses were lower than the secretion at 3 mM glucose, resulting in 18% suppression of average release. The repetitive glucagon pulses were antisynchronous to coincident pulses of insulin and somatostatin. The resulting greater than 20-fold variations of the insulin to glucagon ratio might be essential for minute-to-minute regulation of the hepatic glucose production.
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- Hellman, Bo, et al.
(författare)
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Insulinoscillationer--en kliniskt betydelsefull rytmik. Diabeteslakemedel bor oka den pulsatila komponenten av insulinfrisattningen
- 2007
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Ingår i: Läkartidningen. - 0023-7205. ; 104:32-33, s. 2236-2239
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Tidskriftsartikel (refereegranskat)abstract
- The concentration of circulating insulin oscillates with periods of 3-6 min due to pulsatile release of the hormone from the pancreas. Pulsatile insulin secretion from the individual * cell is driven by slow cycles of Ca2+ elevation due to periodic depolarisation. The Ca2+ oscillations of individual * cells in the islets of Langerhans are entrained into a common rhythm by gap junctional coupling and diffusible factors. Autonomic ganglia coordinate the oscillatory activity of the million islets in the pancreas. ATP binding to purinoceptors causes pronounced Ca2+ spikes that are important for synchronizing the *-cells within and among islets in the pancreas. Inhibition of purinergic P2Y1 receptors selectively abolishes pulsatile insulin release without reducing the average rate of secretion. The insulin oscillations are particularly important for the liver. This organ is also exposed to oscillating levels of glucagon. The latter oscillations are in opposite phase allowing maximal exposure to insulin when the glucagon concentration is at minimum.
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- Hellman, Bo, et al.
(författare)
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Isolated mouse islets respond to glucose with an initial peak of glucagon release followed by pulses of insulin and somatostatin in antisynchrony with glucagon
- 2012
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 417:4, s. 1219-1223
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies of isolated human islets have shown that glucose induces hormone release with repetitive pulses of insulin and somatostatin in antisynchrony with those of glucagon. Since the mouse is the most important animal model we studied the temporal relation between hormones released from mouse islets. Batches of 5-10 islets were perifused and the hormones measured with radioimmunoassay in 30 s fractions. At 3 mM glucose, hormone secretion was stable with no detectable pulses of glucagon, insulin or somatostatin. Increase of glucose to 20 mM resulted in an early secretory phase with a glucagon peak followed by peaks of insulin and somatostatin. Subsequent hormone secretion was pulsatile with a periodicity of 5 min. Cross-correlation analyses showed that the glucagon pulses were antisynchronous to those of insulin and somatostatin. In contrast to the marked stimulation of insulin and somatostatin secretion, the pulsatility resulted in inhibition of overall glucagon release. The cytoarchitecture of mouse islets differs from that of human islets, which may affect the interactions between the hormone-producing cells. Although indicating that paracrine regulation is important for the characteristic patterns of pulsatile hormone secretion, the mouse data mimic those of human islets with more than 20-fold variations of the insulin/glucagon ratio. The data indicate that the mouse serves as an appropriate animal model for studying the temporal relation between the islet hormones controlling glucose production in the liver.
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- Salehi, S Albert, et al.
(författare)
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Absence of adenosine A(1) receptors unmasks pulses of insulin release and prolongs those of glucagon and somatostatin
- 2009
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Ingår i: Life Sciences. - : Elsevier BV. - 0024-3205 .- 1879-0631. ; 85:11-12, s. 470-476
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Extracellular ATP modulates pulsatile release of insulin, glucagon and somatostatin by activating P2Y(1) receptors. The present study examines if adenosine via A(1) receptors (A(1)R) interferes with pulsatile islet hormone release. Main methods: Pancreas was perfused in mice expressing or lacking the A(1) receptor and the hormones measured with radioimmunoassay. Cytoplasmic Ca2+ was recorded in isolated beta-cells using the fura-2 indicator. Key findings: Addition of 10 mu M adenosine removed the Ca2+ transients supposed to coordinate the insulin release pulses. This effect of adenosine was counteracted by 100 nM of the A(1)R antagonist DPCPX. In situ perfusion of the pancreas indicated two phases of islet hormone release when glucose was raised from 3.3 to 16.7 mM. The first phase was characterized by a brief dip followed by a peak which was more pronounced for insulin and somatostatin than for glucagon. The second phase was markedly affected by knock out of A(1)R. The wild-type AIR (+/+) mice, usually lacked statistically verified insulin pulses but generated antisynchronous glucagon and somatostatin pulses with half-widths of 4 min. In the A(1)R (-/-) mice time-average release of insulin during the second phase was almost three times higher than in the controls and 30% of the hormone was released as distinct pulses with half-widths of 3 min. The absence of the AIR receptor resulted in 50% prolongation of the pulse cycles of glucagon and somatostatin and loss of their antisynchronous relationship. Significance: The A(1)R receptor is important both for the amplitude (insulin) and duration (glucagon and somatostatin) of islet hormone pulses. (C) 2009 Elsevier Inc. All rights reserved.
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- Salehi, S Albert, et al.
(författare)
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Pulses of somatostatin release are slightly delayed compared with insulin and antisynchronous to glucagon
- 2007
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 144:1-3, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- It was early proposed that somatostatin-producing delta-cells in pancreatic islets have local inhibitory effects on the release of insulin and glucagon. Recent observations that pulses of insulin and glucagon are antisynchronous make it important to examine the temporal characteristics of glucose-induced somatostatin release. Analysis of 30 s fractions from the perfused rat pancreas indicated that increase of glucose from 3 to 20 mmol/l results in initial suppression of somatostatin release followed by regular 4-5 min pulses. During continued exposure to 20 mmol/l glucose, the pulses of somatostatin overlapped those of insulin with a delay of 30 s. Somatostatin and glucagon pulses were coupled in antisynchronous fashion (phase shift 2.4 +/- 0.2 min), supporting the idea that the delta-cells have a local inhibitory effect on glucagon release. It was possible to remove the pulses of somatostatin and glucagon with maintenance of the insulin rhythmicity by addition of I mu mol/l of the P2Y(1) receptor antagonist MRS 2179.
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