Modulation of proinsulin messenger RNA after partial pancreatectomy in rats. Relationships to glucose homeostasis.

Orland, Matthew J.; Chyn, R; Permutt, M. A.

doi:10.1172/jci111924

Cited by 48 publications

(39 citation statements)

References 44 publications

(53 reference statements)

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“…Hence in islets from non-diabetic rats long-term hyperglycaemia tended to decrease insulin mRNA. These observations are in line with previous observations [27]. Conversely in n-STZ islets normoglycaemia markedly decreased the insulin gene expression.…”

Section: Discussionsupporting

confidence: 93%

Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats

Eizirik¹,

Grill²,

Inoue³

et al. 1994

Diabetologia

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Summary Animals with NIDDM display abnormal glucose regulation of insulin secretion and biosynthesis. We tested reversibility of abnormal regulation by normoglycaemia using an islet transplantation technique. Inbred non-diabetic and neonatally STZ diabetic rats (n-STZ) were used. Transplantations insufficient to normalize the blood glucose levels (200 islets under kidney capsule) were performed from diabetic to normal (D-N) and from diabetic to diabetic (D-D), as well as from normal to normal (N-N) and from normal to diabetic (N-D) rats. Four weeks after transplantation, graft bearing kidneys were isolated and perfused with Krebs-Henseleit bicarbonate buffer to measure insulin secretion in response to 27.8 mmol/1 glucose and 10 mmol/1 arginine. Four weeks of normoglycaemia failed to restore glucose-induced insulin secretion from n-STZ islets (glucose induced increment: -1.7 + 2. 351-357]Key words Animal models NIDDM, insulin secretion, insulin mRNA, cytochrome b mRNA, islets of Langerhans.The neonatally STZ diabetic rat (n-STZ) is an animal model of NIDDM [review 1, 2]. In n-STZ insulin secretion is markedly abnormal at adult age despite only mild or moderate hyperglycaemia [1,2]. In particular, the insulin reponse to glucose is reduced out of proportion to the decrease in beta-cell mass. Responses to non-metabolised secretagogues, such as L-arginine or phosphodiesterase inhibitors, are however relatively preserved. This pattern of abnormalities bears resem-

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Section: Discussionsupporting

confidence: 93%

Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats

Eizirik¹,

Grill²,

Inoue³

et al. 1994

Diabetologia

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“…For example, in this study the pancreatic remnant 4 weeks after 50% pancreatectomy in rats exhibited a 2.8-fold increase in proinsulin mRNA (islet area x proinsulin mRNA density), compared with a 2-fold increase in proinsulin mRNA observed with dot-blot hybridization 3 weeks after 50% pancreatectomy (14). Although measurements of proinsulin mRNA after hyperglycemic clamping have not been reported previously, the in vivo increase in proinsulin mRNA observed here is consistent with the in vitro increase in insulin gene expression in isolated islets exposed to high glucose concentration (15,16).…”

Section: Discussionmentioning

confidence: 46%

Molecular and cellular responses of islets during perturbations of glucose homeostasis determined by in situ hybridization histochemistry.

Chen

Komiya

Inman

et al. 1989

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

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We have evaluated in situ hybridization histochemistry as a means of estimating simultaneously the level of prohormone mRNA and the dimensions of rat pancreatic islets. Localization of the 27-mer 32P-labeled oligonucleotide probes for rat proinsulin I, glucagon, and prosomatostatin I corresponded with localization of antibodies to the three hormones. In normal rats subjected to chronic hyperglycemic clamping, the density of the proinsulin mRNA signal increased 54%, islet size and number increased =100%, while proglucagon mRNA signal was reduced 81%. Resection of 50% of the pancreas increased proinsulin mRNA 36% and proglucagon mRNA 500%; islet area doubled and islet number increased 50%. In 150-day-old diabetic ob/ob mice, there was an 18-fold expansion in islet area, a 4-fold increase in islet number, but no increase in insulin gene expression. In insulin-dependent streptozotocin-treated diabetic rats, islet area and number were profoundly reduced; insulin deprivation failed to raise proinsulin mRNA in surviving beta cells above control levels. Proglucagon mRNA was high despite the hyperglycemia but was reduced by insulin within 1 hr, suggesting that insulin regulates glucagon gene expression or is required for its regulation by glucose. In situ hybridization of rat islets provides a valid semiquantitative index of insulin and glucagon biosynthesis and of islet dimensions and reveals that normal but not diabetic islets meet increased insulin demand by increasing both number and biosynthetic activity of beta cells.Normal islets of Langerhans secrete sufficient insulin to maintain the plasma glucose in the normal range during metabolic stress. This compensatory response could involve either an increase of insulin biosynthesis and secretion or an expansion of beta cell mass or both. Since currently employed techniques do not permit quantitative assessment of these components of the compensatory response in the same pancreas, we have evaluated in situ hybridization histochemistry as a means of estimating simultaneously the molecular mRNA and the cellular responses to increased need for insulin production. METHODSExperimental Groups and Designs. Pancreata were obtained from intact or Wistar rats after a 5-day hyperglycemic clamp or partial pancreatectomy from spontaneously hyperglycemic ob/ob mice from insulin-deprived streptozotocintreated diabetic Wistar rats and from appropriate controls. Hyperglycemia was maintained by infusing 50% (wt/vol) glucose at 51-58 mg/min per kg of body weight through Silastic tubing (Dow) previously implanted in an external jugular vein. After 5 days the pancreas was excised under sodium pentothal anesthesia and was processed for in situ hybridization. Age-matched controls received 5% glucose.In other Wistar rats, a 50% distal pancreatectomy was performed under sodium pentothal anesthesia (1). Four weeks later the remnant was resected under anesthesia. The proximal half of intact pancreata from normal Wistar rats served as controls.Pancreata of diabetic ob/ob mice of ages 60 an...

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“…After a prolonged glucose exposure, however, it is regulated via the insulin gene transcription (Orland et al, 1985;Permutt & Rotwein, 1983;Poitout et al, 2006). Both transcriptional and translational regulation of insulin biosynthesis is essential to maintain the intracellular stores of insulin on a long term basis.…”

Section: The Pancreatic -Cell As a Target Of Estrogens And Xenoestromentioning

confidence: 99%

The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

Nadal

Alonso-Magdalena

Soriano

et al. 2009

Molecular and Cellular Endocrinology

263

187

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. The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes. Molecular and Cellular Endocrinology, Elsevier, 2009, 304 (1-2) Please cite this article as: Nadal, A., Alonso-Magdalena, P., Soriano, S., Quesada, I., Ropero, A.B., The pancreatic ␤-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes, Molecular and Cellular Endocrinology (2008), doi:10.1016/j.mce.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. THE PANCREATIC -CELL AS A TARGET OF ESTROGENS AND XENOESTROGENS: IMPLICATIONS FOR BLOOD GLUCOSE HOMEOSTASIS AND DIABETESAngel Rosen & Spiegelman, 2006;Fritsche et al., 2008). During the fasting state, insulin remains at low levels because plasma glucose concentration is low. In this situation, the levels of the counter-regulatory hormones, glucagon, adrenaline and corticosteroids are increased to promote hepatic glucose production. In contrast, insulin, the only hormone in the body able to decrease blood glucose levels, is increased during the fed state. Insulin decreases blood glucose by promoting adipocyte and muscle glucose uptake, as well as by preventing the liver from producing glucose by suppressing glycogenolysis and gluconeogenesis (Fritsche et al., 2008). neurotransmitters, hormones and nutrients, among which glucose is the most important.Normally, in response to short glucose stimulation, insulin biosynthesis is regulated by the increased translation of the preproinsulin transcript. After a prolonged glucose exposure, however, it is regulated via the insulin gene transcription (Orland et al., 1985;Permutt & Rotwein, 1983;Poitout et al., 2006). Both transcriptional and translational regulation of insulin biosynthesis is essential to maintain the intracellular stores of insulin on a long term basis.The secretory response of -cells depends on their electrical activity. This consists of oscillations of the membrane potential that range from electrically silent periods to depolarised plateaus on which Ca 2+ -action potentials originate (Rorsman et al., 2000).The classical stimulus-secretion coupling that drives insulin release involves the closure of K ATP channels by increasing the intracellular ATP/ADP ratio (Ashcroft et al., 1984) and diadenosine polyphosphates concentration (DPs) (Ripoll et al., 1996) oscillatory pattern is originated (Nadal et al., 1999;Santos et al., 1991;Valdeolmillos et al., 1989), which triggers a pulsatile insulin secretion (Barbosa et al., 1998;Gilon et al., 1993;Dyachok et al., 2008). Estrogens, estrogen receptors and blood glucose homeostasisT...

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Modulation of proinsulin messenger RNA after partial pancreatectomy in rats. Relationships to glucose homeostasis.

Cited by 48 publications

References 44 publications

Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats

Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats

Molecular and cellular responses of islets during perturbations of glucose homeostasis determined by in situ hybridization histochemistry.

The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

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