Biomedical subjects

Kenji Kangawa

Publications and source records attributed to Kenji Kangawa.

At least 235 records · Page 13Linked to original sources

PubMed2002

Aldosterone augments adrenomedullin production without stimulating pro-adrenomedullin N-terminal 20 peptide secretion in vascular smooth muscle cells.

OBJECTIVE: Both adrenomedullin (AM) and pro-adrenomedullin N-terminal 20 peptide (PAMP), processed from the same precursor of prepro-adrenomedullin (preproAM), have differential biological properties; AM dilates blood vessels and presumably affects the vascular remodeling, while PAMP inhibits catecholamine secretion. Since aldosterone has been shown to be involved in vascular remodeling, we examined the effects of aldosterone on AM and PAMP secretion and preproAM gene expression in human aortic vascular smooth muscle cells (VSMC). METHODS: AM and PAMP secreted from human VSMC incubated with aldosterone were measured by radioimmunoassay, and preproAM gene expression was evaluated by quantitative polymerase chain reaction. RESULTS: Cultured human VSMC secreted both AM and PAMP into the media, while the secretion rate of AM was much higher than that of PAMP. Aldosterone increased preproAM gene expression in the cultured VSMC in a dose-dependent fashion following incubation for 48 h, with a concomitant increase in AM secretion from the cells, but PAMP secretion remained unchanged. Aldosterone-stimulated AM secretion was significantly reduced by spironolactone. Reverse-phase high-performance liquid chromatography analyses showed that immunoreactive AM secreted from the VSMC untreated or treated with aldosterone emerged at the point of human AM(1-52)-NH2. CONCLUSIONS: AM production was stimulated by aldosterone in cultured human VSMC without an increase in PAMP secretion, suggesting a possible role of AM in modulating vascular remodeling by aldosterone.

Adrenomedullin↗

PubMed2002

Intravenous adrenomedullin in myocardial function and energy metabolism in patients after myocardial infarction.

This study investigated the effects of adrenomedullin on left ventricular myocardial contraction and relaxation, coronary blood flow, and myocardial oxygen consumption in comparison with those of atrial natriuretic peptide (ANP). Fourteen patients who had had myocardial infarctions were randomly assigned to receive IV infusion of adrenomedullin (0.05 microg/kg/min) or ANP (0.05 microg/kg/min). Both adrenomedullin and ANP significantly decreased left ventricular systolic pressure (-17 mm Hg, -13 mm Hg, respectively, both p < 0.05). The increase in cardiac index by adrenomedullin (+31%) was significantly greater than that by ANP (+16%). Adrenomedullin significantly increased an index of myocardial contractility, Emax (2.5 +/- 0.3 mm Hg-3.7 +/- 0.3 mm Hg/ml, p < 0.05) and shortened an index of myocardial relaxation, Tau (52 +/- 5 ms-48 +/- 4 ms, p < 0.05). In contrast, ANP did not significantly alter either parameter. In addition, adrenomedullin, but not ANP, significantly increased coronary sinus blood flow (73 +/- 10 ml/min-86 +/- 10 ml/min, p < 0.05). Adrenomedullin did not increase myocardial oxygen consumption. Unlike ANP, IV administration of adrenomedullin enhanced left ventricular myocardial contraction and improved left ventricular relaxation without increasing myocardial oxygen consumption in patients who had had a myocardial infarction.

Adrenomedullin↗

PubMed2002

Vasodilatory effect of ghrelin, an endogenous peptide from the stomach.

Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which is identified as an endogenous ligand for GH secretagogues receptor. Although both ghrelin and its specific receptor are expressed in blood vessels, the cardiovascular effects of ghrelin remain unknown. To clarify whether ghrelin has a vasodilatory effect in humans, the response of forearm blood flow (FBF) to intra-arterial infusion of ghrelin was examined in eight healthy volunteers using a plethysmograph. In addition, hormonal responses to ghrelin were studied. Ghrelin increased FBF in a dose-dependent manner. Pretreatment with NG-monomethyl-l-arginine (l-NMMA), a nitric oxide synthase inhibitor, did not inhibit the FBF response to ghrelin, although l-NMMA significantly inhibited GH release. Serum insulin-like growth factor-I (IGF-I) level was not altered by ghrelin administration. Plasma cyclic guanosine 3', 5'-monophosphate level, a second messenger of nitric oxide, was also not altered. These results suggest that ghrelin has vasodilatory effects possibly through GH/IGF-I/nitric oxide-independent mechanisms.

Adult↗

PubMed2002

Local delivery of single low-dose of C-type natriuretic peptide, an endogenous vascular modulator, inhibits neointimal hyperplasia in a balloon-injured rabbit iliac artery model.

C-type natriuretic peptide (CNP) is an endogenous vascular modulator. In addition to vasodilation, CNP exerts multifunctions including anti-thrombus and anti-proliferation actions against vascular smooth muscle cells and myofibroblasts. Therefore, CNP is a potential therapeutic agent for the prevention of restenosis following angioplasty. The current study investigated whether local delivery of CNP, even at microgram levels about three orders of magnitude lower than doses (high milligram levels) used for systemic administration in the previous study, attenuates neointimal hyperplasia. The rabbit iliac artery was denuded, and then CNP (100 microg, n = 5) or control vehicle (n = 5) was administered locally over 20 min, via a local drug delivery catheter. During drug delivery, blood pressure was monitored with a high-fidelity micromanometer catheter. There was no significant decrease in arterial pressure immediately after the CNP administration. Four weeks after the treatment, computer-assisted morphometric analysis revealed significant reduction in the intimal area (CNP 0.44 +/- 0.27 versus control 0.96 +/- 0.20 mm2, p < 0.01), but no changes in the medial area (CNP 0.93 +/- 0.23 versus control 0.79 +/- 0.29 mm2, p = NS). This resulted in a significant decrease in the ratio of the intimal area to the medial area in CNP-treated vessels compared with control vessels (CNP 0.45 +/- 0.26 versus control 1.40 +/- 0.66, p < 0.05). Local delivery of a single low dose of CNP effectively inhibits neointimal hyperplasia with a minimal likelihood of compromising hemodynamics. Considering its multipotent actions and its role as an important regulator of the vascular system, this treatment may have a therapeutic advantage for clinical use.

Animals↗

PubMed2002

Ghrelin: a novel peptide for growth hormone release and feeding regulation.

PURPOSE OF REVIEW: A novel peptide hormone, ghrelin, has been identified from the stomach and recognized as an important regulator of growth hormone release and energy homeostasis. It is interesting to note that the stomach may play an important role in not only digestion but also pituitary growth hormone release and central feeding regulation. Thus, we summarize the recent findings on the mechanism of these effects induced by ghrelin. RECENT FINDINGS: The coadministration of ghrelin and growth hormone releasing hormone was found to have a synergistical effect on pituitary growth hormone secretion. The infusion of growth hormone releasing hormone in rats resulted in a significant increase in pituitary gene expression of ghrelin and its receptor system, suggesting that this system in the pituitary gland could modulate the regulation of growth hormone secretion by growth hormone releasing hormone. Ghrelin promoted the production of orexigenic neuropeptides (neuropeptide Y and agouti-related protein) in the hypothalamic arcuate nuclei and activated the neurons which produce these orexigenic neuropeptides, resulting in an increase in feeding and body weight. Gastric acid release and pancreatic protein secretions were also regulated by ghrelin through vagal and intrapancreatic neuronal activation, respectively. It is possible that ghrelin may participate in the regulation of cell proliferation, glucose homeostasis, and the immune system. SUMMARY: Ghrelin, secreted from the stomach, modulates growth hormone release and feeding promotion. Further elucidation of the mechanisms of ghrelin effects will help to improve the diagnosis and treatment of eating disorders and disturbed conditions of nutritional homeostasis.

Animals↗

PubMed2002

Plasma ghrelin and desacyl ghrelin concentrations in renal failure.

Ghrelin is a novel hormone that possesses growth hormone (GH)-releasing, cardiovascular, and metabolic activities. Ghrelin is a unique acylated polypeptide, and the naked peptide, desacyl ghrelin, does not have the activity. This study examines plasma ghrelin concentrations in 41 patients with mild to severe renal diseases. Two kinds of radioimmunoassays were used: amino-terminal immunoreactivity represents ghrelin alone (N-IR), and carboxyl-terminal immunoreactivity corresponds to the sum of both ghrelin and desacyl ghrelin (C-IR). In all subjects, the plasma N-IR was much smaller than the C-IR, indicating that desacyl ghrelin predominates over ghrelin in the circulation. The plasma C-IR, but not N-IR, was significantly correlated with the serum creatinine level and was increased 2.8-fold in patients with end-stage renal disease compared with those in patients with normal renal function. The plasma GH concentration was significantly correlated with the plasma N-IR and the C-IR, as well as with the serum creatinine level. Bilateral nephrectomy in mice caused marked increase in the plasma C-IR without significant changes in the local C-IR and ghrelin mRNA level in the stomach, which is the main site of ghrelin production. These findings suggest that circulating ghrelin concentrations play a role in the regulation of blood GH concentrations and that the kidney is an important site for clearance and/or degradation of desacyl ghrelin. Furthermore, elevation of blood GH levels in renal failure seems to be caused by a mechanism other than alteration in the circulating ghrelin concentration.

Adult↗

PubMed2002

Ghrelin and the regulation of food intake and energy balance.

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is synthesized principally in the stomach and is released in response to acute and chronic changes in nutritional state. In addition to having a powerful effect on the secretion of growth hormone, ghrelin stimulates food intake and transduces signals to hypothalamic regulatory nuclei that control energy homeostasis. Thus, it is interesting to note that the stomach may play an important role in not only digestion but also pituitary growth hormone release and central feeding regulation. We summarize recent findings on the integration of ghrelin into neuroendocrine networks that regulate food intake and energy balance.

Animals↗

PubMed2002

Renoprotective effect of chronic adrenomedullin infusion in Dahl salt-sensitive rats.

The present study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in hypertensive renal failure and the mechanism by which chronic adrenomedullin infusion exerts its effects. Dahl salt-sensitive rats and Dahl salt-resistant rats were fed a high salt diet starting at 6 weeks of age. Recombinant human adrenomedullin or vehicle was infused for 7 weeks in 11-week-old Dahl salt-sensitive rats. Dahl salt-resistant rat was used as a control. After 7 weeks, untreated Dahl salt-sensitive rats were characterized by decreased kidney function, abnormal morphological findings, increased hormone levels, increased renal tissue angiotensin II levels, and altered mRNA expressions of transforming growth factor beta (TGF-beta) and components of the renin-angiotensin system compared with Dahl salt-resistant rats. Chronic adrenomedullin treatment significantly improved renal function (serum creatinine -87%, creatinine clearance +114%, urinary protein excretion -59%) and histological findings (glomerular injury score -54%) without changing mean arterial pressure compared with untreated Dahl salt-sensitive rats. Interestingly, long-term human adrenomedullin infusion decreased the endogenous rat adrenomedullin level (-97%) with a slight increase of human adrenomedullin level. Chronic adrenomedullin treatment also significantly inhibited the increase of plasma renin concentration (-269%), aldosterone level (-82%), and renal tissue angiotensin II levels (-60%). Furthermore, adrenomedullin infusion significantly decreased the increases of mRNA expressions of TGF-beta (- 63%), angiotensin-converting enzyme (-137%), renin (-230%), and angiotensinogen (-38%) in renal cortex. These results suggest that increased endogenous adrenomedullin plays a compensatory role in chronic hypertensive renal failure and that long-term adrenomedullin infusion has renoprotective effects in this type of hypertension model, partly via inhibition of the circulating and renal renin-angiotensin system.

Adrenomedullin↗

PubMed2002

Long-term adrenomedullin infusion improves survival in malignant hypertensive rats.

Previous studies have demonstrated that adrenomedullin has inhibitory effects on the proliferation and DNA synthesis of mesangial cells and vascular smooth muscle cells in vitro and that plasma adrenomedullin levels are markedly elevated in malignant hypertension. This study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in malignant hypertensive rats. We studied the following 3 groups: control Wistar Kyoto rats, deoxycorticosterone acetate-salt spontaneously hypertensive rats, and adrenomedullin-treated deoxycorticosterone acetate-salt spontaneously hypertensive rats. Chronic adrenomedullin infusion using an osmotic minipump was started simultaneously with deoxycorticosterone acetate-salt treatment. After 3 weeks of the treatment, malignant hypertensive rats were characterized by higher blood pressure, kidney weight, urinary protein excretion, glomerular injury score, plasma renin concentration, aldosterone level, endogenous rat plasma adrenomedullin level, renal cortical tissue angiotensin II level, angiotensin-converting enzyme mRNA level, and transforming growth factor-beta1 mRNA level in the renal cortex, and by lower creatinine clearance, compared with the control rats. Chronic adrenomedullin infusion significantly improved these parameters (kidney weight -6.5%, urinary protein excretion -63.8%, glomerular injury score -38.3%, plasma renin concentration -52.4%, aldosterone -23.2%, rat adrenomedullin -28.6%, renal angiotensin II -28.1%, renal angiotensin-converting enzyme mRNA -38.3%, renal transforming growth factor-beta1 mRNA -56.2%, and creatinine clearance +20.5%) without significant reduction of mean arterial pressure (-4%). Kaplan-Meier survival analysis showed that adrenomedullin infusion significantly prolonged survival time. These results suggest that subdepressor dose of chronic adrenomedullin infusion has renoprotective effects in this malignant hypertension model, at least in part, via inhibition of the circulating and intrarenal renin-angiotensin system.

Adrenomedullin↗

PubMed2002

Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin.

Ghrelin is an acylated peptide, whose lipid modification is essential for its biological activities. Previous studies demonstrated that it strongly stimulates GH release and has a potent orexigenic action. Meanwhile, there is enough evidence showing that feeding states influence plasma ghrelin levels. Fasting stimulates ghrelin secretion, and feeding reduces plasma ghrelin levels. In this study we examined the regulation of plasma ghrelin by fasting in genetically obese animals considering its molecular forms. Plasma levels of active form of ghrelin as well as those of total ghrelin were reduced in ob/ob and db/db mice compared with those in their control mice. Zucker fatty (fa/fa) rats also showed lower plasma ghrelin levels by fasting than the control rats. Insulin-induced hypoglycemia, however, stimulated ghrelin secretion in the fasted fatty rats. Moreover, glucose injection was revealed to reduce plasma ghrelin levels in rats. The effect of the severity of obesity on secretory regulation of ghrelin was also studied. Older fatty rats showed low plasma ghrelin levels even after 48-h fasting. These data suggest that the short-term secretory regulation of total ghrelin and the active form of ghrelin is delayed in obese animals and that blood glucose levels may be involved in the delayed regulation.

Aging↗

PubMed2002

Adrenomedullin inhibits doxorubicin-induced cultured rat cardiac myocyte apoptosis via a cAMP-dependent mechanism.

We previously reported that adrenomedullin produced by cardiac myocytes acts as a local modulator in some cardiac disorders. However, the role of adrenomedullin (AM) in cardiomyocyte apoptosis remains to be clarified. The present study investigated the effect of AM on doxorubicin-induced cardiac myocyte apoptosis. Doxorubicin increased the number of cells with pyknotic nuclei and lactate dehydrogenase release, and AM dose-dependently (10(-10)-10(-8)6 M) inhibited these increases produced by doxorubicin. Treatment with AM also suppressed doxorubicin-induced DNA fragmentation and caspase-3 activation. 8-Bromo-cAMP, a cAMP analog, mimicked these antiapoptotic effects of AM. An AM/calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) and a protein kinase A inhibitor H89 attenuated the antiapoptotic effect of AM. CGRP-(8-37) and H89 had no apoptotic effect alone, but accelerated doxorubicin-induced apoptosis. Under serum-free conditions, AM secretion into the culture medium and expression of AM mRNA were significantly increased after treatment with doxorubicin. Hydrogen peroxide scavenger catalase and antioxidant N-acetyl-L-cysteine inhibited the doxorubicin-mediated increase in AM secretion and its gene expression. These results indicate that AM inhibits doxorubicin-induced cardiac myocyte apoptosis through a cAMP-dependent mechanism and suggest that augmented production of AM by doxorubicin has an endogenous antiapoptotic effect. AM, as an autocrine factor, may play a protective role against cardiomyocyte injury by doxorubicin.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2002

Chicken ghrelin: purification, cDNA cloning, and biological activity.

In this study, we report the purification, cDNA cloning, and characterization of the novel growth hormone-releasing peptide, ghrelin, in the chicken (Gallus gallus). Chicken ghrelin is composed of 26 amino acids (GSSFLSPTYKNIQQQKDTRKPTARLH) and possesses 54% sequence identity with human ghrelin. The serine residue at position 3 (Ser(3)) is conserved between the chicken and mammalian species, as its acylation by either n-octanoic or n-decanoic acid. Chicken ghrelin mRNA is predominantly expressed in the stomach, where it is present in the proventriculus but absent in the gizzard. Using RT-PCR analysis, low levels of expression were also detectable in brain, lung, and intestine. Administration of chicken ghrelin increases plasma GH levels in both rats and chicks, with a potency similar to that of rat or human ghrelin. In addition, chicken ghrelin also increases plasma corticosterone levels in growing chicks at a lower dose than in mammals. The present results indicate that the stimulatory effect of ghrelin on GH secretion is evolutionarily conserved, whereas its effect on adrenal function seems to be unique in the chicken.

Amino Acid Sequence↗

PubMed2002

Goldfish ghrelin: molecular characterization of the complementary deoxyribonucleic acid, partial gene structure and evidence for its stimulatory role in food intake.

Complementary deoxyribonucleic acid (cDNA) encoding goldfish preproghrelin was identified using rapid amplification of the cDNA ends (RACE) and reverse transcription (RT)-polymerase chain reaction (PCR). The 490 bp cDNA encodes a 103 amino acid preproghrelin which has a 26 amino acid signal region, 19 amino acid mature peptide and a 55 amino acid C-terminal peptide region. The mature peptide region of goldfish ghrelin has two putative cleavage sites and amidation signals (GRR); one after 12 amino acids and the other after 19 amino acids. The serine (S) in the second amino acid position in the "active core" of ghrelin is substituted with threonine (T). The goldfish ghrelin gene has four exons and three short introns and resembles the human ghrelin gene. Ghrelin messenger RNA (mRNA) expression was detected in the brain, pituitary, intestine, liver, spleen and gill by RT-PCR followed by Southern blot analysis, and in the intestine by Northern blot. Intracerebroventricular (ICV) injection of n-octanoylated goldfish ghrelin (1-19) stimulates food intake in goldfish.

Amino Acid Sequence↗

PubMed2002

Ghrelin expression in islet cell tumors: augmented expression of ghrelin in a case of glucagonoma with multiple endocrine neoplasm type I.

Ghrelin is a 28-amino acid peptide that regulates GH release together with GHRH and somatostatin. The expression of ghrelin has been detected in the stomach, small intestine, hypothalamus, pituitary gland, kidney, placenta, and testis. Recently it was reported that ghrelin is present in pancreatic alpha-cells and that it stimulates insulin secretion. In this study, we examined the ghrelin expression in two cases of glucagonoma and two cases of insulinoma by Northern blot analysis and immunohistochemistry. Ghrelin expression was identified in a case of glucagonoma associated with multiple endocrine neoplasm type I both by Northern blot analysis using total RNA and by immunohistochemistry, although the plasma ghrelin level was not elevated. This is the first case of tumor in which ghrelin gene expression was detected by Northern blot analysis using total RNA.

Adenoma, Islet Cell↗

PubMed2002

Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion.

Ghrelin, a novel GH-releasing peptide isolated from human and rat stomach, stimulates food intake and GH secretion. We determined plasma ghrelin concentrations in patients with simple obesity, anorexia nervosa, and type 2 diabetes mellitus by RIA. We also studied plasma ghrelin responses to glucose load and meal intake and obtained a 24-h profile of circulating ghrelin in humans. Plasma ghrelin concentrations in patients with simple obesity and anorexia nervosa were lower and higher, respectively, than those of healthy subjects with normal body weight. Among those with type 2 diabetes mellitus, obese patients had lower and lean patients higher fasting plasma ghrelin concentrations than normal-weight patients. Fasting plasma ghrelin concentration was negatively correlated with body mass index in both nondiabetic and diabetic patients. Plasma ghrelin concentrations of normal subjects decreased significantly after oral and iv glucose administration; a similar response was also observed in diabetic patients after a meal tolerance test, reaching a nadir of 69% of the basal level after the meal. Circulating plasma ghrelin showed a diurnal pattern with preprandial increases, postprandial decreases, and a maximum peak at 0200 h. This study demonstrates that nutritional state is a determinant of plasma ghrelin in humans. Ghrelin secretion is up-regulated under conditions of negative energy balance and down-regulated in the setting of positive energy balance. These findings suggest the involvement of ghrelin in the regulation of feeding behavior and energy homeostasis.

Adult↗

PubMed2002

Plasma levels of adrenomedullin and atrial and brain natriuretic peptides in the general population: their relations to age and pulse pressure.

Adrenomedullin (AM) and atrial and brain natriuretic peptides (ANP and BNP) exert vasodilator and natriuretic actions and are thought to share roles in counteracting the progression of hypertension or heart failure as circulating or locally-acting hormones. However, little data is available with regard to their roles in subjects who have no apparent cardiovascular diseases. The present study was carried out to identify the factors that affect plasma levels of AM, ANP and BNP in the general population. We measured the plasma levels of AM, ANP and BNP in 184 local residents who had a scheduled regular health checkup, and compared the findings with those for other clinical parameters. Univariate analyses showed that the plasma levels of AM, ANP and BNP were significantly correlated with age. The plasma levels of ANP and BNP were also significantly correlated with systolic blood pressure (SBP) and with pulse pressure (PP), an indicator of the stiffness of the great vessels. Multivariate analyses conducted using a stepwise method revealed that age was a significant, independent variable for the plasma levels of AM, ANP and BNP. In addition, PP was a significant factor for the plasma levels of ANP and BNP, while the plasma AM was significantly associated with body mass index (BMI). Thus, the plasma levels of AM, ANP and BNP all increased in association with aging, and those of ANP and BNP increased in association with PP, suggesting possible relationships between the plasma levels and age-related changes in the cardiovascular system.

Adrenomedullin↗

PubMed2002

Plasma ghrelin levels during exercise in healthy subjects and in growth hormone-deficient patients.

OBJECTIVE: To characterise plasma levels of the recently identified endogenous ligand for the GH secretagogue receptor (ghrelin) during submaximal aerobic exercise in healthy adults and in GH-deficient adults. DESIGN: Eight healthy males (mean+/-s.e. age, 40.8+/-2.9 years) and eight hypopituitary males with verified GH deficiency (mean+/-s.e. age, 40.8+/-4.7 years) underwent a baseline test of their peak aerobic capacity (VO(2) peak) and lactate threshold (LT) on a cycle ergometer, as well as an evaluation of body composition. The patients were then studied on two occasions in random order when they exercised for 45 min at their LT. On one occasion, GH replacement had been discontinued from the evening before, whereas on the other occasion they received their evening GH in addition to an intravenous infusion of GH (0.4 IU) during exercise the following day. The healthy subjects exercised at their LT on one occasion without GH. RESULTS: The patients were significantly more obese and had lower VO(2) max (corrected for body weight) and LT as compared with the control subjects. Exercise induced a peak in serum GH concentrations after 45 min in the control group (11.43+/-3.61 microg/l). Infusion of GH in the patients resulted in a peak level after 45 min, whereas no increase was detected when exercising without GH (9.77+/-2.40 (GH) vs 0.11+/-0.07 microg/l (no GH)). Plasma ghrelin levels did not change significantly with time in either study, and no correlations were detected between ghrelin levels and parameters such as GH and IGF-I levels, age or body composition. Plasma ghrelin levels were significantly lower during the study period with GH as compared with the study with no GH. CONCLUSIONS: Submaximal aerobic exercise of an intensity sufficient to stimulate GH release was not associated with significant alterations in plasma ghrelin concentrations, which indicated that systemic ghrelin is not involved in the exercise-induced stimulation of GH secretion. The observation that ghrelin levels were lower during GH replacement suggests that GH may feedback-inhibit systemic ghrelin release.

Adult↗

PubMed2002

Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion.

Ghrelin, a novel growth hormone-releasing peptide isolated from human and rat stomach, is a 28-amino acid peptide with a posttranslational acylation modification that is indispensable for stimulating growth hormone secretion by increasing intracellular Ca(2+) concentration. It also functions in the regulation of feeding behavior, energy metabolism, and gastric acid secretion and motility. Using two different antibodies against the NH(2)- and COOH-terminal regions of ghrelin, we studied its localization in human and rat pancreas by immunohistochemistry. Ghrelin-immunoreactive cells were identified at the periphery of pancreatic islets in both species. Ghrelin co-localized exclusively with glucagon in rat islets, indicating that it is produced in alpha-cells. We identified ghrelin and des-acyl ghrelin in the rat pancreas using reverse-phase high-performance liquid chromatography combined with two radioimmunoassays. We also detected mRNA encoding ghrelin and its receptor in the rat pancreatic islets. Ghrelin increased the cytosolic free Ca(2+) concentration in beta-cells and stimulated insulin secretion when it was added to isolated rat pancreatic islets. These findings indicate that ghrelin may regulate islet function in an endocrine and/or paracrine manner.

Animals↗