Heikki A. Koistinen
A5114374611- Genetic Associations and Epidemiology
- Adipose Tissue and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Nutrition, Genetics, and Disease
- Metabolism, Diabetes, and Cancer
- Regulation of Appetite and Obesity
- Bioinformatics and Genomic Networks
- Pancreatic function and diabetes
- Genetic Mapping and Diversity in Plants and Animals
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Peroxisome Proliferator-Activated Receptors
- Genetics and Physical Performance
- Genetic and phenotypic traits in livestock
- Birth, Development, and Health
- Lipid metabolism and disorders
- Cancer-related molecular mechanisms research
- Diabetes Treatment and Management
- Diabetes and associated disorders
- Lipoproteins and Cardiovascular Health
- RNA Research and Splicing
- Muscle Physiology and Disorders
- Genomics and Rare Diseases
- Diet and metabolism studies
Finnish Institute for Health and Welfare
2016-2025
Minerva Foundation
2015-2024
University of Helsinki
2015-2024
Helsinki University Hospital
2015-2024
Erasmus University Rotterdam
2015
Karolinska Institutet
2002-2009
Institute for Molecular Medicine Finland
2009
Steno Diabetes Centers
2009
Broad Institute
2009
Massachusetts Institute of Technology
2009
The incidence of hematologic cancers increases with age. These are associated recurrent somatic mutations in specific genes. We hypothesized that such would be detectable the blood some persons who not known to have disorders.
To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects European ancestry after imputation using 1000 Genomes multiethnic reference panel. Promising signals were followed up in additional sets (of 14,545 or 7,397 38,994 71,604 subjects). We identified 13 novel T2D-associated loci (P < 5 × 10-8), including variants near GLP2R, GIP, HLA-DQA1...
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations rare (with minor allele frequencies less than 0.5%) in 4 genes at exome-wide significance, including a series more 30 SLC30A8 alleles conveys protection against T2D, 12 gene sets, those...
Abstract We identified signaling pathways by which IL-6 regulates skeletal muscle differentiation and metabolism. Primary human cells were exposed to (25 ng/ml either acutely or for several days), small interfering RNA gene silencing was applied measure glucose fat Chronic exposure increased myotube fusion formation the mRNA expression of transporter 4, peroxisome proliferator activated receptor (PPAR)α, PPARδ, PPARγ, PPARγ coactivator 1, glycogen synthase, myocyte enhancer factor 2D,...
AMP-activated protein kinase (AMPK) activation by AICAR (5-amino-imidazole carboxamide riboside) is correlated with increased glucose transport in rodent skeletal muscle via an insulin-independent pathway. We determined vitro effects of insulin and/or exposure on and cell-surface GLUT4 content from nondiabetic men type 2 diabetes. a dose-dependent manner healthy subjects. Insulin to similar extent control In contrast, insulin- AICAR-stimulated responses were impaired subjects Importantly,...
Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. Elevated plasma levels of IL-6 are observed in insulin-resistant states. Interestingly, also increase during exercise, with skeletal muscle being the predominant source. Thus, has been suggested promote insulin-mediated glucose utilization. In this study, we determined direct effects on transport and signal transduction human muscle. Skeletal strips were prepared from vastus lateralis biopsies obtained 22...
Abstract Type 2 diabetes (T2D) results from the combined effects of genetic and environmental factors on multiple tissues over time. Of >100 variants associated with T2D related traits in genome-wide association studies (GWAS), >90% occur non-coding regions, suggesting a strong regulatory component to risk. Here understand how status, metabolic variation influence gene expression, we analyse skeletal muscle biopsies 271 well-phenotyped Finnish participants glucose tolerance ranging...
We integrate comeasured gene expression and DNA methylation (DNAme) in 265 human skeletal muscle biopsies from the FUSION study with >7 million genetic variants eight physiological traits: height, waist, weight, waist-hip ratio, body mass index, fasting serum insulin, plasma glucose, type 2 diabetes. find hundreds of genes DNAme sites associated as well thousands (eQTM). that controlling for heterogeneity tissue/muscle fiber reduces number trait associations, long-range eQTMs (>1 Mb) are...
Abstract Hundreds of thousands genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops disease (termed penetrance) is unknown for virtually all them. Additionally, clinical utility common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral type 2 diabetes case-control study and 38,566 participants UK Biobank, whom genotype array data were also available), we...
Leptin is an adipocyte-derived peptide hormone regulating energy balance in experimental animals.Although the physiological function of leptin humans still unclear, its secretion closely related to fat mass adult humans.To examine how fetal growth correlates with levels at birth, umbilical cord venous blood sample was obtained delivery from 50 term newborn infants.Twenty-eight infants had birth weights appropriate for gestational age (AGA; mean Ϯ SEM, 3362 90 g; relative weight, Ϫ0.08 0.2...
Abstract The remarkable adaptive and regenerative capacity of skeletal muscle is regulated by several transcription factors pathways. Here we show that the factor Prox1 an important regulator myoblast differentiation slow fibre type. In both rodent human muscles specifically expressed in fibres stem cells called satellite cells. activates NFAT signalling pathway necessary sufficient for maintenance gene program Using lineage-tracing Prox1-positive differentiate into fibres. Furthermore,...