nach oben

Diabetologia

Erschienen in:

01.06.2006 | Article

Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats

verfasst von: T. Irako, T. Akamizu, H. Hosoda, H. Iwakura, H. Ariyasu, K. Tojo, N. Tajima, K. Kangawa

Erschienen in: Diabetologia | Ausgabe 6/2006

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

Ghrelin, a stomach-derived hormone, functions in multiple biological processes, including glucose metabolism and cellular differentiation and proliferation. In this study, we examined whether early treatment with ghrelin can regenerate beta cells of the pancreas in an animal model of diabetes mellitus, the n0-STZ model, in which neonatal rats are injected with streptozotocin (STZ) at birth.

Methods

Following administration of ghrelin to n0-STZ rats from postnatal days 2 to 8, we examined beta cell mass, mRNA expression levels of insulin and of pancreatic and duodenal homeobox 1 (Pdx1) gene, and pancreatic morphology on days 21 and 70. In addition, we investigated the effects of ghrelin on beta cell replication.

Results

By day 21, ghrelin treatment increased pancreatic expression of insulin and Pdx1 mRNA in n0-STZ rats. The number of replicating cells was also significantly increased in the ghrelin-treated n0-STZ model. At day 70, n0-STZ rats exhibited hyperglycaemia, despite slight increases in plasma insulin levels. Ghrelin treatment resulted in the improvement of plasma glucose levels, which were associated with normal plasma insulin levels. Pancreatic insulin mRNA and protein levels were significantly increased in ghrelin-treated n0-STZ model animals.

Conclusions/interpretation

These findings suggest that ghrelin promotes regeneration of beta cells in STZ-treated newborn rats. Thus, early administration of ghrelin may help prevent the development of diabetes in disease-prone subjects after beta cell destruction.

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660PubMedCrossRef

van der Lely AJ, Tschop M, Heiman ML, Ghigo E (2004) Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 25:426–457PubMedCrossRef

Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB (2004) Ghrelin—a hormone with multiple functions. Front Neuroendocrinol 25:27–68PubMedCrossRef

Lee HM, Wang G, Englander EW, Kojima M, Greeley GH Jr (2002) Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 143:185–190PubMedCrossRef

Adeghate E, Ponery AS (2002) Ghrelin stimulates insulin secretion from the pancreas of normal and diabetic rats. J Neuroendocrinol 14:555–560PubMedCrossRef

Arosio M, Ronchi CL, Gebbia C, Cappiello V, Beck-Peccoz P, Peracchi M (2003) Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. J Clin Endocrinol Metab 88:701–704PubMedCrossRef

Broglio F, Gottero C, Benso A et al (2003) Effects of ghrelin on the insulin and glycemic responses to glucose, arginine, or free fatty acids load in humans. J Clin Endocrinol Metab 88:4268–4272PubMedCrossRef

Guan XM, Yu H, Palyha OC et al (1997) Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 48:23–29PubMedCrossRef

Volante M, Allia E, Gugliotta P et al (2002) Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 87:1300–1308PubMedCrossRef

10.

Chanoine JP, Wong AC (2004) Ghrelin gene expression is markedly higher in fetal pancreas compared to fetal stomach: effect of maternal fasting. Endocrinology 145:3813–3820PubMedCrossRef

11.

Kim MS, Yoon CY, Jang PG et al (2004) The mitogenic and anti-apoptotic actions of ghrelin in 3T3-L1 adipocytes. Mol Endocrinol 18:2291–2301PubMedCrossRef

12.

Thompson NM, Gill DA, Davies R et al (2004) Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 145:234–242PubMedCrossRef

13.

Tourrel C, Bailbe D, Meile MJ, Kergoat M, Portha B (2001) Glucagon-like peptide-1 and exendin-4 stimulate beta-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age. Diabetes 50:1562–1570PubMedCrossRef

14.

Tsuji K, Taminato T, Usami M et al (1988) Characteristic features of insulin secretion in the streptozotocin-induced NIDDM rat model. Metabolism 37:1040–1044PubMedCrossRef

15.

Wang RN, Bouwens L, Kloppel G (1994) Beta-cell proliferation in normal and streptozotocin-treated newborn rats: site, dynamics and capacity. Diabetologia 37:1088–1096PubMedCrossRef

16.

Wang RN, Bouwens L, Kloppel G (1996) Beta-cell growth in adolescent and adult rats treated with streptozotocin during the neonatal period. Diabetologia 39:548–557PubMedCrossRef

17.

Watada H, Kajimoto Y, Miyagawa J et al (1996) PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin. Diabetes 45:1826–1831PubMedCrossRef

18.

Ferber S, Halkin A, Cohen H et al (2000) Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 6:568–572PubMedCrossRef

19.

Kojima H, Nakamura T, Fujita Y et al (2002) Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin. Diabetes 51:1398–1408PubMedCrossRef

20.

Matsuoka T, Kajimoto Y, Watada H et al (1995) Expression of CD38 gene, but not of mitochondrial glycerol-3-phosphate dehydrogenase gene, is impaired in pancreatic islets of GK rats. Biochem Biophys Res Commun 214:239–246PubMedCrossRef

21.

Petrik J, Reusens B, Arany E et al (1999) A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II. Endocrinology 140:4861–4873PubMedCrossRef

22.

Sun L, Lee J, Fine HA (2004) Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury. J Clin Invest 113:1364–1374PubMed

23.

Davidson EJ, Morris LS, Scott IS et al (2003) Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia. Br J Cancer 88:257–262PubMedCrossRef

24.

Garofano A, Czernichow P, Breant B (2000) Impaired beta-cell regeneration in perinatally malnourished rats: a study with STZ. FASEB J 14:2611–2617PubMedCrossRef

25.

Gnanapavan S, Kola B, Bustin SA et al (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87:2988–2991PubMedCrossRef

26.

Wierup N, Svensson H, Mulder H, Sundler F (2002) The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept 107:63–69PubMedCrossRef

27.

Broglio F, Gottero C, Benso A et al (2003) Ghrelin and the endocrine pancreas. Endocrine 22:19–24PubMedCrossRef

28.

Date Y, Nakazato M, Hashiguchi S et al (2002) Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 51:124–129PubMedCrossRef

29.

Colombo M, Gregersen S, Xiao J, Hermansen K (2003) Effects of ghrelin and other neuropeptides (CART, MCH, orexin A and B, and GLP-1) on the release of insulin from isolated rat islets. Pancreas 27:161–166PubMedCrossRef

30.

Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L (2004) Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci USA 101:2924–2929PubMedCrossRef

31.

Cassoni P, Ghe C, Marrocco T et al (2004) Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines. Eur J Endocrinol 150:173–184PubMedCrossRef

32.

Volante M, Allia E, Fulcheri E et al (2003) Ghrelin in fetal thyroid and follicular tumors and cell lines: expression and effects on tumor growth. Am J Pathol 162:645–654PubMed

33.

Zhang W, Lin TR, Hu Y et al (2004) Ghrelin stimulates neurogenesis in the dorsal motor nucleus of the vagus. J Physiol 559:729–737PubMed

34.

Gown AM, Jiang JJ, Matles H et al (1996) Validation of the S-phase specificity of histone (H3) in situ hybridization in normal and malignant cells. J Histochem Cytochem 44:221–226PubMed

35.

Muskhelishvili L, Latendresse JR, Kodell RL, Henderson EB (2003) Evaluation of cell proliferation in rat tissues with BrdU, PCNA, Ki-67(MIB-5) immunohistochemistry and in situ hybridization for histone mRNA. J Histochem Cytochem 51:1681–1688PubMed

36.

Hayashida T, Nakahara K, Mondal MS et al (2002) Ghrelin in neonatal rats: distribution in stomach and its possible role. J Endocrinol 173:239–245PubMedCrossRef

37.

Poykko SM, Kellokoski E, Horkko S, Kauma H, Kesaniemi YA, Ukkola O (2003) Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 52:2546–2553PubMedCrossRef

Titel: Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats
verfasst von: T. Irako
T. Akamizu
H. Hosoda
H. Iwakura
H. Ariyasu
K. Tojo
N. Tajima
K. Kangawa
Publikationsdatum: 01.06.2006
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 6/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0226-3

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2006

Enhanced soluble CD40L in patients with the metabolic syndrome: relationship with in vivo thrombin generation

Early foetal programming of hepatic gluconeogenesis: glucocorticoids strike back

Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects

Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats

Excess mortality in incident cases of diabetes mellitus aged 15 to 34 years at diagnosis: a population-based study (DISS) in Sweden