Delta Cell Hyperplasia in Adult Goto-Kakizaki (GK/MolTac) Diabetic Rats

Alán, Lukáš; Olejár, Tomáš; Cahová, Monika; Zelenka, Jaroslav; Berková, Zuzana; Smětáková, Magdalena; Saudek, F; Matěj, Radoslav; Ježek, Petr

doi:10.1155/2015/385395

Cited by 19 publications

(19 citation statements)

References 50 publications

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“…The number of δ‐cells was increased in early stages of the syndrome and the elevated volume density coincided with massive β‐cell necrosis . Additionally, in diabetes, a local overproduction of somatostatin could diminish β‐cell viability and might contribute to the deterioration of β‐cell mass through paracrine effects as speculated by Alán et al . who found a hyperplasia of δ‐cells in pancreatic islets of GK rats.…”

Section: Discussionmentioning

confidence: 85%

“…Many studies have focused on the influence of insulin and glucagon in the pathophysiology of diabetes. Diabetes is characterized by both, peripheral insulin resistance and/or pancreatic β‐cell dysfunction as well as hyperglucagonemia . Nevertheless, an impact of somatostatin in the pathogenesis of the disease also has to be taken into consideration.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, a study on GK rats demonstrated a higher expression of somatostatin mRNA combined with an increased number of δ‐cells in pancreatic islets of GK rats. Predominantly in elderly animals, a disturbed cytoarchitecture occurred with irregular β‐cells accompanied by δ‐cell hyperplasia . Furthermore, the pancreatic content of somatostatin is increased in GK rats and spontaneously diabetic ob/ob and db/db mice .…”

Section: Discussionmentioning

confidence: 99%

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Distribution and density of melatonin receptors in human main pancreatic islet cell types

Zibolka

Bazwinsky-Wutschke

Mühlbauer

et al. 2018

Journal of Pineal Research

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Recent investigations of our group established that melatonin modulates hormone secretion of pancreatic islets via melatonin receptor types MT1 and MT2. Expression of MT1 and MT2 has been shown in mouse, rat, and human pancreatic islets as well as in the β-, α-, and δ-cell lines INS-1, αTC1.9, and QGP-1. In view of these earlier investigations, this study was performed to analyze in detail the distribution and density of melatonin receptors on the main islet cell types in human pancreatic tissue obtained from nondiabetic and type 2 diabetic patients. Immunohistochemical analysis established the presence of MT1 and MT2 in β-, α-, and δ-cells, but notably, with differences in receptor density. In general, the lowest MT1 and MT2 receptor density was measured in α-cells compared to the 2 other cell types. In type 2 diabetic islets, MT1 and MT2 receptor density was increased in δ-cells compared to normoglycemic controls. In human islets in batch culture of a nondiabetic donor, an increase of somatostatin secretion was observed under melatonin treatment while in islets of a type 2 diabetic donor, an inhibitory influence could be observed, especially in the presence of 5.5 mmol/L glucose. These data suggest the following: i) cell-type-specific density of MT1 and MT2 receptors in human pancreatic islets, which should be considered in context of the hormone secretion of islets, ii) the influence of diabetes on density of MT1 and MT2 as well as iii) the differential impact of melatonin on somatostatin secretion of nondiabetic and type 2 diabetic islets.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Distribution and density of melatonin receptors in human main pancreatic islet cell types

Zibolka

Bazwinsky-Wutschke

Mühlbauer

et al. 2018

Journal of Pineal Research

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“…U naših ekspreimentalnih životinja je konstatovana i hiperplazija D ćelija koje sekretuju somatostatin. Hiperplazija somatostatinskih ćelija je opisana u dijabetesu tip 2 kod ljudi i pacova 27 .…”

Section: Diskusijaunclassified

Endocrine pancreas in rats chronically treated with Cadmium

Jancic¹,

Rančić²,

Zujovic³

et al. 2018

Materia medica

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Kadmijum (Cd) je mekan srebtrnasto-beli metal, jedan od 126 prioritetnih zagađivača, a svrstan je i u grupu humanih karcinogena I kategorije.Cilj rada je mikromorfološko i funkcionalno ispitivanje endokrinog pankreasa pacova hronično tretiranih kadmijumom. Za istraživanje su korišćeni beli Wistar pacovi ženskog pola, starosti 35-37 dana, težine 120-140 g.Ukupno je bilo 22 životinje koje su podeljene na kontrolnu (n=11) i eksperimentalnu grupu (n=11). Eksperimentalna grupa je svakodnevno tretirana sa 15mg/kg CdCl2 rastvorenog u pijaćoj vodi. Kontrolna grupa nije bila podvrgnuta nikakvom tretmanu. Svi pacovi su čuvani u kontrolisanim laboratorijskim uslovima. Posle tri meseca, sve životinje su žrtvovane. Tkivo pankreasa je rutinski obrađeno i kalupljeno u parafi n. Na 4μm presecima su primenjene HE i imunohistohemijska ABC metoda sa antitelima na: chromogranin A, insulin,glucagon,somatostatin, pankreasni polipeptid, i peptid YY. U životinja eksperimentalne grupe su nađene guste, hiperplastične B ćelije koje zaposedaju skoro čitavu površinu insule. Prisutna je i hiperplazija A ćelija sa izraženom funkcionalnom aktivnošću. Osim po obodu hiperplastičnih insula, pojedinačne A ćelije se nalaze i u acinusima u kojima je njihova aktivnost znatno povećana. Zapažen je povećan mitotski indeks i odsustvo citoplazmatskih produžetka D ćelija. Izražena je hiperplazija PP ćelija, sa znacima kako morfološkog tako i funkcionalnog polimorfi zma. Prisustvo PP ćelija je evidentirano i u hiperplastičnom i displastičnom epitelu većih duktusa. Samo u životinja eksperimentalne grupe smo našli ćelije koje sekretuju peptid YY. Ove ćelije imaju identičnu topografi ju kao i A ćelije, ali je njihov broj znatno manji. Hronično izlaganje kadmijumu remeti strukturu i funkciju endokrinog pankreasa.Sve pankreasne endokrine ćelije su pogođene.

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“…Somatostatin is a peptide hormone released by the delta cells of the pancreas that suppresses the release of insulin and several counterregulatory hormones, including glucagon, catecholamines, growth hormone and cortisol [19]. In humans and in animal models, diabetes causes somatostatin levels to rise systemically [20,21] and within the islets themselves [20,[22][23][24]. By antagonising somatostatin receptor (SSTR)2 with a selective SSTR2 antagonist (SSTR2a), PRL-2903, we have demonstrated that glucagon and corticosterone responses to insulin-induced hypoglycaemia are improved [25,26], as is the depth and duration of hypoglycaemia [27].…”

Section: Introductionmentioning

confidence: 99%

Glucagon responses to exercise-induced hypoglycaemia are improved by somatostatin receptor type 2 antagonism in a rat model of diabetes

et al. 2016

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Aims/hypothesis Regular exercise is at the cornerstone of care in type 1 diabetes. However, relative hyperinsulinaemia and a blunted glucagon response to exercise promote hypoglycaemia. Recently, a selective antagonist of somatostatin receptor 2, PRL-2903, was shown to improve glucagon counterregulation to hypoglycaemia in resting streptozotocin-induced diabetic rats. The aim of this study was to test the efficacy of PRL-2903 in enhancing glucagon counterregulation during repeated hyperinsulinaemic exercise. Methods Diabetic rats performed daily exercise for 1 week and were then exposed to saline (154 mmol/l NaCl) or PRL-2903, 10 mg/kg, before hyperinsulinaemic exercise on two separate occasions spaced 1 day apart. In the following week, animals crossed over to the alternate treatment for a third hyperinsulinaemic exercise protocol. Results Liver glycogen content was lower in diabetic rats compared with control rats, despite daily insulin therapy (p < 0.05). Glucagon levels failed to increase during exercise with saline but increased three-to-six fold with PRL-2903 (all p < 0.05). Glucose concentrations tended to be higher during exercise and early recovery with PRL-2903 on both days of treatment; this difference did not achieve statistical significance (p > 0.05). Conclusions/interpretation PRL-2903 improves glucagon counterregulation during exercise. However, liver glycogen stores or other factors limit the prevention of exercise-induced hypoglycaemia in rats with streptozotocin-induced diabetes.

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Delta Cell Hyperplasia in Adult Goto-Kakizaki (GK/MolTac) Diabetic Rats

Cited by 19 publications

References 50 publications

Distribution and density of melatonin receptors in human main pancreatic islet cell types

Distribution and density of melatonin receptors in human main pancreatic islet cell types

Endocrine pancreas in rats chronically treated with Cadmium

Glucagon responses to exercise-induced hypoglycaemia are improved by somatostatin receptor type 2 antagonism in a rat model of diabetes

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