Role of apolipoprotein C‐III overproduction in diabetic dyslipidaemia

Autor: Nina Lundbom, Linda Andersson, Sanni Söderlund, Juhani Kahri, Haihong Zhou, Martin Adiels, Marja-Riitta Taskinen, Annika Thorsell, Kirsi H. Pietiläinen, Antti Hakkarainen, Niina Matikainen, Elias Björnson, Carina Sihlbom, Chris J. Packard, Jan Borén
Přispěvatelé: Research Programs Unit, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, HUS Abdominal Center, Endokrinologian yksikkö, HUS Internal Medicine and Rehabilitation, Marja-Riitta Taskinen Research Group, Department of Medicine, HUS Medical Imaging Center, Department of Diagnostics and Therapeutics, University of Gothenburg, University of Helsinki, Department of Neuroscience and Biomedical Engineering, Merck, University of Glasgow, Aalto-yliopisto, Aalto University
Rok vydání: 2019
Předmět:
Blood Glucose
Male
Very low-density lipoprotein
Apolipoprotein B
Endocrinology
Diabetes and Metabolism
apolipoprotein C-III
Type 2 diabetes
030204 cardiovascular system & hematology
CORONARY EVENTS
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
OF-FUNCTION MUTATIONS
Glucose homeostasis
RISK
2. Zero hunger
PLASMA
biology
Area under the curve
Middle Aged
Postprandial Period
REMNANT CHOLESTEROL
TRIGLYCERIDE-RICH LIPOPROTEIN
3. Good health
Postprandial
Female
lipids (amino acids
peptides
and proteins)
type 2 diabetes
VLDL
medicine.drug
medicine.medical_specialty
LOW-DENSITY-LIPOPROTEIN
stable isotopes
030209 endocrinology & metabolism
METABOLISM
03 medical and health sciences
Internal medicine
Internal Medicine
medicine
Humans
Hypoglycemic Agents
Triglycerides
ta217
Aged
Dyslipidemias
Apolipoprotein C-III
Triglyceride
Liraglutide
business.industry
medicine.disease
lipoproteins
Diabetes Mellitus
Type 2
chemistry
kinetics
3121 General medicine
internal medicine and other clinical medicine
biology.protein
business
CIII
Zdroj: Diabetes, Obesity and Metabolism. 21:1861-1870
ISSN: 1463-1326
1462-8902
Popis: openaire: EC/H2020/305707/EU//RESOLVE Aims: To investigate how apolipoprotein C-III (apoC-III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC-III, and whether improvement of glycaemic control using the glucagon-like peptide-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics. Materials and Methods: Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5- 2 H 3 ]leucine using ultrasensitive mass spectrometry techniques. We compared apoC-III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non-diabetic subjects. Liver fat content, subcutaneous abdominal and intra-abdominal fat were determined using proton magnetic resonance spectroscopy. Results: Improved glycaemic control by liraglutide therapy for 16 weeks significantly reduced apoC-III secretion rate (561 ± 198 vs. 652 ± 196 mg/d, P = 0.03) and apoC-III levels (10.0 ± 3.8 vs. 11.7 ± 4.3 mg/dL, P = 0.035) in subjects with type 2 diabetes. Change in apoC-III secretion rate was significantly associated with the improvement in indices of glucose control (r = 0.67; P = 0.009) and change in triglyceride area under the curve (r = 0.59; P = 0.025). In line with this, the apoC-III secretion rate was higher in subjects with type 2 diabetes compared with BMI-matched non-diabetic subjects (676 ± 208 vs. 505 ± 174 mg/d, P = 0.042). Conclusions: The results reveal that the secretion rate of apoC-III is associated with elevation of triglyceride-rich lipoproteins in subjects with type 2 diabetes, potentially through the influence of glucose homeostasis on the production of apoC-III.
Databáze: OpenAIRE
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