Seppo M Pöykkö

University of Oulu, Oulu, Oulu, Finland

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Publications (11)47.08 Total impact

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    ABSTRACT: Ghrelin, a peptide hormone from stomach, stimulates food intake and decreases fat utilization. Ghrelin binds to growth hormone secretagogue receptor (GHSR). GHSR density has been shown to be upregulated in atherosclerotic lesions, but the relationship between ghrelin concentration and atherosclerosis has not yet been studied. We, therefore, characterized the association between ghrelin concentration and carotid artery intima-media thickness (IMT) in a population-based cohort of 1024 middle-aged (40-60 years) men and women. Intima-media thickness and the number of atherosclerotic plaques were determined ultrasonographically. Fasting plasma ghrelin concentrations were analysed using RIA-kit (PhoenixPeptide). There was a positive association between mean IMT and ghrelin concentration in the analysis of males before and after adjustments for the traditional risk factors of atherosclerosis [age, systolic blood pressure, LDL cholesterol, body mass index (BMI), and smoking (ancova, P = 0.004 and P = 0.007, respectively)]. However, no such association was found in females (P = 0.985 and P = 0.915). There was no correlation between ghrelin and CRP concentrations or ghrelin and smoking. Ghrelin concentrations and carotid artery atherosclerosis are positively associated in males even after adjustment for the commonly recognized risk factors of atherosclerosis. Experimental and prospective studies are warranted to elucidate the role of ghrelin in atherosclerosis.
    Journal of Internal Medicine 08/2006; 260(1):43-52. · 6.46 Impact Factor
  • Olavi Ukkola, Seppo M Pöykkö, Y Antero Kesäniemi
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    ABSTRACT: Low ghrelin concentration has been associated with several features of metabolic syndrome (MS), but the relationship between ghrelin concentration and MS as a cluster of metabolic aberrations has not yet been studied. To analyse whether ghrelin concentration is associated with MS. Fasting plasma ghrelin concentrations of the population-based cohort of 1037 middle-aged men and women were analysed using a commercial radioimmunoassay kit (Phoenix Peptide). MS was determined using the new International Diabetes Federation criteria. The prevalence of MS was 37.2%. The ghrelin concentrations were decreased in subjects with MS (635 pg/mL) compared to those without MS (687 pg/mL) (P=0.001). Ghrelin levels decreased with an increase in the number of metabolic abnormalities. Low ghrelin was a statistically significant predictor of MS in logistic regression analysis (P=0.005) so that the subjects in the 1st ghrelin quartile were at higher risk of having MS compared to the subjects in the 4th quartile (OR=1.82, 95% CI: 1.27-2.60, P=0.001). This association remained statistically significant after adjustment for age and sex (OR=1.76, 95% CI: 1.24-2.55, P=0.002). Metabolic syndrome is associated with low ghrelin levels suggesting a relationship of ghrelin in the metabolic disturbances of MS.
    Annals of Medicine 02/2006; 38(4):274-9. · 5.09 Impact Factor
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    ABSTRACT: Ghrelin is a novel peptide hormone that has GH releasing activity and also other endocrine and metabolic functions. The purpose of this study was to investigate the effects of estrogen replacement therapy on plasma active ghrelin levels in 64 hysterectomized postmenopausal women receiving peroral estrogen (PE) or transdermal estrogen therapy for 6 months. Active ghrelin was measured using commercial RIA. Estrogen therapy increased plasma active ghrelin from 479 +/- 118 to 521 +/- 123 pg/ml (P = 0.002) among all the study subjects. PE therapy increased plasma ghrelin levels from 465 +/- 99 to 536 +/- 104 pg/ml (P = 0.001). Transdermal estrogen therapy did not increase plasma ghrelin levels significantly (from 491 +/- 132 to 509 +/- 138 pg/ml; P = 0.332). The relative changes in plasma ghrelin levels were associated with the relative changes in serum estradiol concentrations (r = 0.299; P = 0.017). During the estrogen therapy, negative associations were found between plasma active ghrelin levels and several plasma lipids (total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, total triglycerides, and very low-density lipoprotein triglycerides). As a conclusion, estrogen replacement therapy increased active plasma ghrelin levels, particularly PE therapy. Additional studies are needed to determine the possible underlying mechanisms.
    Journal of Clinical Endocrinology &amp Metabolism 06/2005; 90(5):2954-63. · 6.43 Impact Factor
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    ABSTRACT: Ghrelin is a natural growth hormone-releasing peptide thought to be involved in the regulation of energy metabolism. The recent studies concerning the association between ghrelin and insulin-like growth factor-I (IGF-I) concentrations have shown either negative correlation or no correlation at all. The aims of this study were to clarify the association between ghrelin and IGF-I concentrations in a large cohort and to characterize whether obesity, insulin resistance and type 2 diabetes affect this association. We analysed fasting plasma ghrelin and IGF-I concentrations of 1,004 middle-aged subjects of the population-based OPERA study. Insulin resistance was estimated using QUICKI. IGF-I concentrations were negatively associated with ghrelin concentrations in the analysis of all subjects before (beta=-0.32, p<0.001) and after adjustments for BMI, insulin levels, sex and age (beta=-0.40, p<0.001). The association was particularly strong in males and in the higher BMI tertiles. The degree of association varied in relation to the glycaemic status: no insulin resistance: r(2)=6.5% (p<0.001), insulin resistance without type 2 diabetes: r(2)=21.0% (p<0.001), type 2 diabetes: r(2)=25.4 (p<0.001). IGF-I levels explained larger proportion (r(2)=9.8%) of the variation in ghrelin concentrations compared to fasting insulin concentration (r(2)=3.0%) and BMI (r(2)=1.5%). There is a negative and independent association between ghrelin and IGF-I concentrations in middle-aged subjects. The interaction between IGF-I and ghrelin is modified by obesity, IR and type 2 diabetes. Further studies are warranted to elucidate the role of ghrelin in the development of these states.
    Diabetologia 03/2005; 48(2):309-16. · 6.49 Impact Factor
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    ABSTRACT: Alterations in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF-I levels. To investigate whether IGF-I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery. Fasting plasma IGF-I concentrations (n=1008) were measured in a large population-based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method. Low IGF-I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C-reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF-I concentrations were positively associated with the mean IMT of women (ss=0.127, P=0.009) whereas the association in men was weaker and negative (ss=-0.088, P=0.034). The 1169A allele was associated with low low-density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women. IGF-I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF-I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.
    Annals of Medicine 02/2005; 37(5):373-82. · 5.09 Impact Factor
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    SEPPO PÖYKKÖ, Biocenter Oulu
    01/2005;
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    ABSTRACT: Ghrelin is a novel 28 amino acid peptide which is reported to have several endocrine and non-endocrine actions. It possesses strong growth hormone (GH)-releasing activity, which is mediated via the GH secretagogue receptor type 1a (GHS-R1a). We hypothesised that there might be functional sequential variations in the GHS-R1a gene affecting phenotypes linked to the GH/insulin-like growth factor-I (IGF-I)-axis. To test our hypothesis we chose patients from our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study with low (n=96) and high (n=96) IGF-I levels, sequenced their GHS-R1a gene exons and performed association studies. We found five single-nucleotide polymorphisms (SNPs) which did not change the amino acid sequence. We were unable to detect associations between the SNPs and the IGF-I plasma concentrations, but instead we showed that SNP 171C>T was associated with the values of the area under the insulin curve (AUCIN) in an oral glucose tolerance test and with IGF-binding protein-1 (IGFBP-1) concentrations (P<0.05). SNP 477G>A was associated with the low density lipoprotein and very low density lipoprotein cholesterol plasma levels and AUCIN values (P<0.05). This study was the first genomic screening of the GHS-R1a gene in a population. It suggests that genetic variations in the GHS-R1a gene are not the main regulators of IGF-I levels. However, the variants may be associated with IGFBP-1 concentrations and insulin metabolism.
    European Journal of Endocrinology 04/2004; 150(4):457-63. · 3.14 Impact Factor
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    ABSTRACT: Experimental studies have suggested that ghrelin plays a role in glucose homeostasis and in the regulation of blood pressure (BP). We therefore assessed the hypothesis that a low ghrelin concentration may be a risk factor for type 2 diabetes and hypertension. We also characterized the effect of the ghrelin Arg51Gln and Leu72Met mutations on ghrelin concentrations in the population-based hypertensive (n = 519) and control (n = 526) cohorts of our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. The fasting plasma ghrelin concentrations of 1,040 subjects were analyzed using the radioimmunoassay method. Insulin sensitivity was assessed using the quantitative insulin sensitivity check index (QUICKI). Ghrelin concentrations were negatively associated with fasting insulin (P < 0.001), systolic (P = 0.026) and diastolic BP (P = 0.018), and the prevalence of type 2 diabetes (P = 0.015) and insulin resistance (P < 0.001) in the multivariate models. In the control cohort, low ghrelin was associated with hypertension (BP >140/90 mmHg) (P = 0.031). The subjects with the ghrelin 51Gln allele had lower ghrelin concentrations than the Arg51Arg homozygotes (P = 0.001). We conclude that low ghrelin is independently associated with type 2 diabetes, insulin concentration, insulin resistance, and elevated BP. Therefore, it might have some role in the etiology of type 2 diabetes and the regulation of BP. The ghrelin Arg51Gln mutation is associated with low plasma ghrelin concentrations.
    Diabetes 10/2003; 52(10):2546-53. · 7.90 Impact Factor
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    ABSTRACT: Experimental studies have suggested that ghrelin, a novel gastrointestinal peptide hormone, could play a role in glucose homeostasis. In addition, ghrelin has been associated with beneficial haemodynamic effects in experimental settings. Since the Arg51Gln mutation changes the carboxyterminal amino acid of the mature hormone and is associated with low ghrelin concentrations, we assessed the hypothesis that Arg51Gln mutation is a risk factor for Type 2 diabetes, impaired glucose tolerance, and hypertension. Blood pressure recordings and oral glucose tolerance test were carried out in the hypertensive ( n=519) and control cohorts ( n=526) of our well-defined OPERA study. The genotypes and plasma IGF-I and IGFBP-1 concentrations of 1031 subjects were analysed. The ghrelin 51Gln allele was a risk factor for Type 2 diabetes, and the effect remained significant after adjustment for age, BMI, and study group (OR=2.53, CI: 1.11-5.75, p=0.027). In addition, the 51Gln allele was a risk factor for hypertension (OR=2.63, CI: 1.37-5.08, p=0.003). 51Gln carriers had lower concentrations of IGF-I and higher concentrations of IGFBP-1 compared to non-carriers. The ghrelin 51Gln allele could increase the risk for Type 2 diabetes and hypertension. The low IGF-I concentrations in 51Gln carriers suggest that the mechanism might be associated with low GH concentrations.
    Diabetologia 05/2003; 46(4):455-8. · 6.49 Impact Factor
  • Olavi Ukkola, Seppo Pöykkö
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    ABSTRACT: Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) that potently stimulates growth hormone (GH) release. The discovery of ghrelin opens up a new regulatory system for GH secretion. Surprisingly, recent studies in rodents suggest that peripherally or centrally administered ghrelin, independent of GH, decreases fat oxidation and increases food intake and adiposity. In addition, plasma ghrelin levels are lower in obese human subjects. Ghrelin might participate in meal initiation and may signal to the hypothalamus when an increase in metabolic efficiency is needed.
    Lakartidningen 06/2002; 99(19):2152-3.
  • Olavi Ukkola, Seppo Pöykkö
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    ABSTRACT: The objective of this paper is to review the current evidence of a novel gastric hormone ghrelin. Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) that potently stimulates growth hormone (GH) release. The discovery of ghrelin opens up a new regulatory system for the GH secretion. Surprisingly, recent studies in rodents suggest that peripherally or centrally administrated ghrelin, independent of GH, decreases fat oxidation and increases food intake and adiposity. In addition, plasma ghrelin levels are lower in obese human subjects. Ghrelin might participate in meal initiation and may signal to the hypothalamus when an increase in the metabolic efficiency is needed. However, the role of ghrelin in the regulation of body weight in humans is unknown. Whether ghrelin's somatotrophic effect surpasses its adipogenic effect in the prolonged administration determines its effect on energy balance. New interesting implications for ghrelin have recently been suggested. For instance, ghrelin's cardiovascular effects might have clinical relevance. Furthermore, ghrelin might be involved in the growth of some neoplasms. In conclusion, ghrelin, a new somatotrophic, orexigenic and adipogenic peptide hormone, links the regulatory systems for growth and energy balance.
    Duodecim; lääketieteellinen aikakauskirja 02/2002; 118(2):133-5.