Browsing by Subject "insuliiniresistenssi"

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  • Vara, Katariina (Helsingfors universitet, 2012)
    The main objective of this thesis was to analyse the impact of dry period energy intake on the intensity of metabolic stress and insulin resistance through changes in gene expression in dairy cows. Calving and beginning of lactation cause a negative energy balance which increases fat mobilization, metabolic stress and insulin resistance. These are intensified by high milk yield and excess energy intake from feed during the dry period. 14 genes were selected for the analysis. These genes encode proteins that are linked to lipogenesis, lipolysis and insulin signaling. The changes in the gene expression of subcutaneous adipose tissue were compared between two groups of eight cows. The control group was fed according to the energy requirements while the test group was fed ad libitum. The biopsies were taken -8d, +1d and +9d from parturition, cDNA was synthesized from them and they were analysed by quantitative PCR and 2-??CT-method. There Expression differences were observed in seven genes within the whole data between biopsy dates. During the period from before to after parturition, differences were identified in the expression of 11 genes within the whole data and the control group, and one gene in the test group. The most significant differences were observed in LEP and SCD genes. Between the groups there was a difference in the gene expression of IRS1 before parturition. This refers to the test group being more insulin resistant. After parturition there were no significant differences found in the gene expressions. The most significant changes observed in this study were as expected in early lactation. In the period between before and after parturition there were bigger changes in the gene expression observed in the control group than in the test group. The results indicate that cows getting more energy from their feed during the dry period are more insulin resistant before parturition.
  • Hovi, Marianne (Helsingfors universitet, 2012)
    The burden of diabetes is increasing globally as the number of people with diabetes reaches over 220 million. Over 90 per cent of these people are suffering from type 2 diabetes. This condition is primarily defined by the chronic increase in blood glucose level or hyperglycemia. Type 2 diabetes is characterized by insulin resistance and is usually associated with abnormal insulin secretion. Insulin resistance is a state where normal amount of blood insulin is inadequate to increase glucose uptake in the most important target tissues of insulin. Numerous reports demonstrate that oversupply of lipids leads to loss of insulin activity and the formation of type 2 diabetes. Protein kinase C (PKC) isozymes comprise a family of serine/threoninekinases, which have a regulatory role in a multiple cellular processes. PKC!-isozyme activity is known to play a role in insulin resistance and therefore in type 2 diabetes. Free fatty acid (FFA) induced insulin gene function inhibition is associated with phosphoinositide dependent kinase1 (PDK1) independent phosphorylation of PKC!-isozyme in the most important insulin target tissues. Phosphorylated PKC!-isozyme causes insulinreceptor gene expression inhibition. Present study is part of a VHH-antibodies related research where the goal is to characterize these antibodies and to find out their effects on protein kinase C. VHH-antibodies are Ilama derived antibodies which contain a single heavy-chain variable domain, that is fully capable of antigen binding. In this work, we studied VHH-antibodies binding to PKC!-isozyme and its functional domains. PKC!-isozyme and its domains were produced in Sf9-insect cells. The binding was studied using Western blot and immunoprecipitation assays. In addition, the binding of 368 VHHantibodies to PKCε-isozyme's domain 2 were studied. With Western blot, it was discovered that E7-VHH-antibody binds to PKCε-isozyme full length and to domain 3. Other VHHantibodies tested in Western blot did not bind to PKCε-isozyme. Seven VHH-antibodies bound to PKCε-isozyme in immunoprecipitation. All of these VHH-antibodies bound to the full length and to domain 3, but not to other domains. In radioligand binding assays none of the VHH-antibodies bound to domain 2 that is the binding site to the endogenous PKCε-isozyme activator diacylglycerol (DAG). The results gathered with these three different methods were in line with each other. As the results gained from Western blot and immunoprecipitation show, all the VHH-antibodies, that bind to PKCε-isozyme, bind to its domain 3. With this study, we succeeded to gather new information about the binding of VHH-antibodies to PKCε-isozyme and its domains. The exact binding site has not been studied with so many VHH-antibodies before this study. Moreover, we also exploited methods that have not been used in this context before.
  • Karlsson, Elina (Helsingfors universitet, 2017)
    The aim of this study was to investigate the effect of cultivated pasture and semi-natural grassland on body condition and insulin sensitivity in horses. The main hypothesis was that the horses would fatten more when grazing on cultivated pasture compared to semi-natural grassland, and that insulin, glucose and non-esterified fatty acid (NEFA) responses to i.v. glucose challenge would indicate higher degree of insulin resistance of these horses. The experiment was carried out between May–September 2014 at a research farm of the former MTT Agrifood Research Finland (now Natural Resources Institute Finland) in Ypäjä. Body weight, body condition score, waist circumference, and fat thickness were measured before and after grazing season. Intravenous glucose tolerance tests (IVGTT) were performed on 16 horses (8 of each group) in May and September. A dose of glucose was administered through a jugular vein catheter. Multiple blood samples were then collected to assess glucose, insulin and NEFA responses. There were no differences between treatments in body measurements, or glucose, insulin, and NEFA responses to IVGTT before grazing. Horses grazing on cultivated pasture had higher body weight, median body condition score and waist circumference compared to horses on semi-natural grassland in September. Slower glucose clearance rate and a smaller decrease in NEFAs during IVGTT was noticed in horses grazing on semi-natural grassland compared to those on cultivated pasture after grazing season. Minimal Model estimates on insulin sensitivity were compromised by the large variation in insulin responses to glucose challenge. Two thirds of the Si estimates were classified as insulin resistant or implausible (extreme insulin resistance or sensitivity). The differences in pasture composition between high-yielding cultivated pasture and semi-natural grassland induced only minor changes in the insulin resistance status of grazing Finnhorse mares. Grazing on the cultivated pasture did not increase the level of peripheral insulin resistance compared to semi-natural grassland or compromise horses’ ability to maintain normal blood glucose concentration in spite of their fattening. Contrary to the hypothesis, horses grazing on semi-natural grassland expressed higher degree of insulin resistance in adipose tissue. Horses were rather insulin resistant already before grazing which may be derived from a possible innate tendency to low insulin sensitivity of Finnhorse.
  • Kivelä, Jemina (Helsingin yliopisto, 2017)
    The association of serum branched chain amino acids with insulin resistance, risk of type 2 diabetes and intake of macronutrients Both type 2 diabetes and insulin resistance have been associated with elevated concentrations of blood branched-chain amino acids (BCAA). However, it is not yet known why blood BCAA levels are elevated in people in an insulin-resistant state or how lifestyle and nutrition may affect blood BCAA concentrations. The aim of this study was to determine whether a high serum BCAA concentration is associated with the risk of developing type 2 diabetes and insulin resistance in men and women with impaired glucose tolerance (IGT). The association between macronutrient intake and serum BCAA concentration was also explored in this study. Serum BCAA concentration was analysed at baseline and after 1 year in 128 men and 279 women participating in the Finnish Diabetes Prevention Study (DPS). At baseline, all participants were middle-aged, had been diagnosed with IGT and were classified as overweight. All participants were monitored for T2D onset by oral glucose tolerance testing annually, over an average period of 9 years. Anthropometric measurements, blood samples and 3-day food diaries were collected at baseline and at year 1. Gender-specific quartiles of baseline BCAA were used to categorize the participants (Q1, Q2, Q3, Q4); Cox regression was used to analyse diabetes risk among the BCAA categories. Linear regression analysis was used to test for an association between BCAA concentration and a homeostatic model of insulin resistance (HOMA-IR) and macronutrient intake. In addition, linear regression analysis was used to test for an association between changes in BCAA concentration from baseline to year 1 and changes of HOMA-IR and macronutrient intake. The models were adjusted for age, education, gender and body mass index. In addition, the intakes of macronutrients were adjusted for energy intake. Serum BCAA concentration at baseline was associated with the development of T2D (Q4 vs. Q1 HR=1.72 [1.07–2.75]; Q3 vs. Q1 HR=1.69 [1.05–2.70]; Q2 vs. Q1 HR=1.06 [0.63–1.77]). BCAA concentration correlated with HOMA-IR (β=0.20; p<0.001) but changes in BCAA concentration was not associated with changes in HOMA-IR. In men, there was an inverse correlation between baseline BCAA and baseline energy intake (β=−0.23; p=0.01), while protein intake relative to energy intake was directly correlated with BCAA concentration (β=0.19; p=0.03), although the correlation was attenuated after adjusting (p=0.05). In women, baseline fat intake was correlated with BCAA (β=0.26; p=0.04), although the correlation was attenuated after adjusting (p=0.08). In women, a change in the intake of saturated fat correlated with a change in BCAA (β=0.17; p=0.04). The results of this study support earlier findings that, in people with IGT, elevated blood BCAA concentration is associated with insulin resistance and the risk of developing type 2 diabetes. This study also showed that the intake of macronutrients is differentially associated with blood BCAA concentration in men and women. Additionally, this study suggests that macronutrient intake may be associated with blood BCAA concentration. Futher studies are required to determine whether macronutrient intake modifies the association between blood BCAA concentration and risk of developing type 2 diabetes.
  • Toivonen, Heli (Helsingin yliopisto, 2019)
    Tiineyden loppuvaiheessa ja laktaatiokauden alussa lypsylehmä käy läpi suuria aineenvaihdunnallisia muutoksia. Lehmän rehun syönti ei suurene riittävän nopeasti maidontuotannon alkaessa ja seurauksena on riittämättömästä energiansaannista johtuva negatiivinen energiatase. Negatiivisen energiataseen takia lehmä joutuu mobilisoimaan rasva- ja valkuaisvarastojaan saadakseen lisää energiaa. Rasvakudosten mobilisointi vapauttaa plasmaan vapaita rasvahappoja (NEFA), joiden pitoisuutta mittaamalla voidaan arvioida lehmien energiatasetta. Plasman NEFA-pitoisuuden liiallinen suureneminen poikimisen aikaan voi johtaa terveysongelmiin, kuten rasvamaksaan ja ketoosiin, jotka voivat aiheuttaa myös taloudellisia menetyksiä. Liiallinen energiansaanti ummessaolokaudella voi pienentää kuiva-aineen syöntiä poikimisen aikaan ja lisätä rasvakudosten mobilisaatiota. Laktaatiokauden alussa märehtijöille on tyypillistä voimistunut insuliiniresistenssi rasvakudoksissa ja lihaksissa, mikä edistää vapaiden rasvahappojen ja aminohappojen mobilisaatiota. Insuliiniresistenssissä haiman tuottaman insuliinin vaikutus on heikentynyt, jolloin insuliinista riippuvaiset kudokset eivät saa riittävästi glukoosia ja lipolyysi lisääntyy. Veren NEFA-pitoisuuden suurentamisen on osoitettu kokeellisesti voimistavan insuliiniresistenssiä ummessaolevilla lypsylehmillä. Ravitsemuksellisilla tekijöillä, kuten rehun kuitupitoisuutta lisäämällä, voidaan pienentää NEFA-pitoisuuden suurenemista ennen poikimista. Tämän tutkimuksen tavoitteena oli selvittää ummessaolokauden karkearehun energiapitoisuuden vaikutusta lypsylehmien rasva- ja valkuaisainevarastojen käyttöön. Tutkimuksessa oli mukana 16 vähintään toista kertaa poikivaa ayrshire-lehmää, jotka jaettiin pareihin kuntoluokan ja odotetun poikimapäivän perusteella. Koe suoritettiin täydellisesti satunnaistettuna lohkokokeena, jossa toisen ryhmän lehmät saivat ummessaolokaudella vapaasti säilörehua ja toisen ryhmän lehmät kuitupitoista seosrehua. Poikimisen jälkeen kummankin ryhmän lehmät saivat samaa säilörehua vapaasti ja väkirehuannosta nostettiin asteittain. Tutkimuksen aikana (8vk ennen poikimista – 8 vk poikimisen jälkeen) lehmiä punnittiin, kuntoluokitettiin, niiltä otettiin verinäytteitä, mitattiin selkälihaksen paksuutta ja niille tehtiin glukoosirasituskoe ennen poikimista ja poikimisen jälkeen. Verinäytteistä määritettiin glukoosi-, insuliini-, BHBA- eli b-hydroksivoihappo-, NEFA- ja 3-MH- eli 3-metyylihistidiinipitoisuudet. Tulosten perusteella ummessaolokauden ruokinnan muuttaminen kuitupitoisemmaksi ja energiaköyhemmäksi ei vaikuttanut suuresti plasman parametreihin eikä lehmien kuntoluokkaan. Ummessaolokauden vapaa säilörehuruokinta ei lisännyt rasvavarastojen mobilisaatiota poikimisen jälkeen, kun säilörehu oli sulavuudeltaan enintään keskinkertaista. Tässä tutkimuksessa suurempi energiansaanti näkyi suuremmassa elopainon suurenemisessa, muttei kuntoluokan muutoksessa ennen poikimista. Plasman insuliinipitoisuus ennen poikimista oli suurempi paljon energiaa saaneilla lehmillä, mikä on havaittu aikaisemmissakin tutkimuksissa. Runsaammin energiaa saaneet lehmät saattavat tämän kokeen tulosten perusteella kompensoida kudostensa insuliiniherkkyyden vähenemistä insuliinin eritystä lisäämällä. Rehun kuitupitoisuuden lisääminen esimerkiksi tekemällä seosrehua säilörehusta ja oljesta vaikuttaa olevan toimiva vaihtoehto pienentää ummessaolevan lehmän energiansaantia liian lihomisen välttämiseksi.