Islet amyloid polypeptide inhibits glucose-stimulated insulin secretion from isolated rat pancreatic islets

Ohsawa, Haruhiko; Kanatsuka, Azuma; Yamaguchi, Tetsuro; Makino, Hideichi; Yoshida, Sho

doi:10.1016/0006-291x(89)92529-1

Cited by 197 publications

(103 citation statements)

References 25 publications

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“…Although this explanation might account for the decrease in glucose-induced insulin secretion, the extent of islet cell loss over the time period from addition of h-IAPP to the end of the study was insufficient to be measurable by quantitative analysis (and certainly less than the ϳ90% decrease in glucose-induced insulin secretion). An alternative explanation is the action of IAPP through its cell surface receptor to inhibit insulin secretion (39). However, any receptor-mediated actions of IAPP would be most evident with r-IAPP that would have remained monomeric in conditions of culture, in contrast to h-IAPP that would have spontaneously formed h-IAPP oligomers.…”

Section: Discussionmentioning

confidence: 99%

Human Islet Amyloid Polypeptide Oligomers Disrupt Cell Coupling, Induce Apoptosis, and Impair Insulin Secretion in Isolated Human Islets

Ritzel¹,

Meier²,

Lin³

et al. 2007

Diabetes

169

154

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Insulin secretion from the 2,000 -3,000 ␤-cells in an islet is a highly synchronized activity with discharge of insulin in coordinate secretory bursts at approximately 4-min intervals. Insulin secretion progressively declines in type 2 diabetes and following islet transplantation. Both are characterized by the presence of islet amyloid derived from islet amyloid polypeptide (IAPP). In the present studies, we examined the action of extracellular human IAPP (h-IAPP) on morphology and function of human islets. Because oligomers of h-IAPP are known to cause membrane disruption, we questioned if application of h-IAPP oligomers to human islets would lead to disruption of islet architecture (specifically cell-to-cell adherence) and a decrease in coordinate function (e.g., increased entropy of insulin secretion and diminished coordinate secretory bursts). Both hypotheses are affirmed, leading to a novel hypothesis for impaired insulin secretion in type 2 diabetes and following islet transplantation, specifically disrupted cell-to-cell adherence in islets through the actions of membrane-disrupting IAPP oligomers. Diabetes 56:65-71, 2007

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Section: Discussionmentioning

confidence: 99%

Human Islet Amyloid Polypeptide Oligomers Disrupt Cell Coupling, Induce Apoptosis, and Impair Insulin Secretion in Isolated Human Islets

Ritzel¹,

Meier²,

Lin³

et al. 2007

Diabetes

169

154

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“…Firstly, the peptide was isolated from pancreatic amyloid deposits [1] suggesting some abnormality associated with its expression. Secondly, the peptide was found to oppose the action of insulin on skeletal muscle preparations [3] and thirdly, it was found to inhibit insulin release [4]. Although there is no wholly satisfactory model for Type 2 diabetes in the rat, dexamethasone and partial streptozotocin treatment produce conditions having elements in common with this condition and these were therefore investigated using the technique of Northern blotting.…”

Section: Discussionmentioning

confidence: 99%

“…This peptide is now known as islet amyloid polypeptide (IAPP) [2], or amylin [3]. IAPP opposes the action of insulin on isolated muscle preparations [3] and inhibits insulin release from rat islets in vitro [4]. Using a cloned DNA probe representing the rat IAPP coding sequence, we have recently found IAPP to be present in the stomach as well as the pancreas [5].…”

mentioning

confidence: 99%

Altered islet amyloid polypeptide (amylin) gene expression in rat models of diabetes

et al. 1989

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Summary. The response of the islet amyloid polypeptide gene to chronic dexamethasone treatment in adult rats was investigated. After 12 daily injections, rats were severely underweight and fasting blood glucose levels were elevated. When pancreatic mRNA was analysed, a 16-fold elevation in islet amyloid polypeptide mRNA was observed with only a fourfold increase in insulin mRNA levels. Pancreatic islet amyloid polypeptide and insulin mRNA levels were also determined 12 days after streptozotocin treatment. In these rats, which were not severely diabetic, the reduction in islet amyloid polypeptide mRNA levels was sixfold less than the reduction in insulin mRNA levels. In both these models of diabetes the ratio of islet amyloid polypeptide to insulin mRNA levels was raised. This would not be expected if the physiological role of islet amyloid polypeptide is as a simple hyperglycaemic agent opposing insulin action or release.Key words: Islet amyloid polypeptide, amylin, Type 2 (noninsulin-dependent) diabetes mellitus, mRNA, streptozotocin, dexamethasone, rat.A 37 amino acid peptide with homology to calcitonin gene related peptide (CGRP) has recently been characterised from the pancreatic amyloid deposits of a Type 2 (non-insulin-dependent) diabetic patient [1] and from an insulinoma [2]. This peptide is now known as islet amyloid polypeptide (IAPP) [2], or amylin [3]. IAPP opposes the action of insulin on isolated muscle preparations [3] and inhibits insulin release from rat islets in vitro [4]. Using a cloned DNA probe representing the rat IAPP coding sequence, we have recently found IAPP to be present in the stomach as well as the pancreas [5]. A variety of evidence thus suggests that this peptide may play an important role in the control of carbohydrate metabolism. We therefore decided to study the expression of the IAPP gene in the rat pancreas after treatment with agents known to affect carbohydrate metabolism. In particular, we wanted to know whether IAPP and insulin levels could be regulated independently and whether induced peripheral insulin resistance would lead to changes in the pancreas which might have relevance to amyloid deposition in man. Materials and methods Drug treatmentsAdult male Wistar rats of 125-150g were divided into 3 groups: (1) controls (n = 5) fed ad libitum on standard rat chow, (2) dexamethasone (n = 5) 2 mg/kg injected i.p. each day for 12 days, and (3) streptozotocin treatment (n =24) 60 mg/kg injected i.v. 12 days prior to analysis. After treatment, rats were starved overnight and killed by cervical dislocation after ether anaesthesia. Blood was taken for glucose measurements and the pancreas was dissected and frozen under liquid nitrogen for RNA extraction. RNA analysisTotal RNA was prepared from the frozen tissues and analysed by Northern blotting with rat IAPP and insulin probes as previously [5]. However, to minimise handling, polyadenylated RNA was not purified in the present experiments and 30 ~g of total RNA was loaded onto each track of these gels. Stringent washing conditi...

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“…Amylin, originally identified in amyloid plaques in the pancreatic islets of Type II diabetics, may be a circulating fl-cell hormone controlled by blood glucose levels. Moreover, amylin itself has been implicated in the pathogenesis of Type II (insulin-resistant) diabetes Ohsawa et al, 1989;Nishi et al, 1990). Thus, an emerging issue is whether amylin and CGRP act on common or distinct receptors, possibly with some degree of cross-talk (Morishita et al, 1990;Nishi et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological characterization of a receptor for calcitonin gene‐related peptide on rat, L6 myocytes

Poyner

Andrew²,

Brown³

et al. 1992

British J Pharmacology

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1 The L6 myocyte cell line expresses high affinity receptors for calcitonin gene-related peptide (CGRP) which are coupled to activation of adenylyl cyclase. The biochemical pharmacology of these receptors has been examined by radioligand binding or adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. 5 The pharmacological profile of the L6 CGRP receptor suggests that it most closely resembles sites on skeletal muscle, cardiac myocytes and hepatocytes. The L6 cell line should be a stable homogeneous model system in which to study CGRP mechanisms and pharmacology.

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Islet amyloid polypeptide inhibits glucose-stimulated insulin secretion from isolated rat pancreatic islets

Cited by 197 publications

References 25 publications

Human Islet Amyloid Polypeptide Oligomers Disrupt Cell Coupling, Induce Apoptosis, and Impair Insulin Secretion in Isolated Human Islets

Human Islet Amyloid Polypeptide Oligomers Disrupt Cell Coupling, Induce Apoptosis, and Impair Insulin Secretion in Isolated Human Islets

Altered islet amyloid polypeptide (amylin) gene expression in rat models of diabetes

Pharmacological characterization of a receptor for calcitonin gene‐related peptide on rat, L6 myocytes

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