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- Laine, Saara, et al.
(författare)
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Effects of Different Exercise Training Protocols on Gene Expression of Rac1 and PAK1 in Healthy Rat Fast- and Slow-Type Muscles.
- 2020
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Rac1 and its downstream target PAK1 are novel regulators of insulin and exercise-induced glucose uptake in skeletal muscle. However, it is not yet understood how different training intensities affect the expression of these proteins. Therefore, we studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on Rac1 and PAK1 expression in fast-type (gastrocnemius, GC) and slow-type (soleus, SOL) muscles in rats after HIIT and MICT swimming exercises.Methods: The mRNA expression was determined using qPCR and protein expression levels with reverse-phase protein microarray (RPPA).Results: HIIT significantly decreased Rac1 mRNA expression in GC compared to MICT (p = 0.003) and to the control group (CON) (p = 0.001). At the protein level Rac1 was increased in GC in both training groups, but only the difference between HIIT and CON was significant (p = 0.02). HIIT caused significant decrease of PAK1 mRNA expression in GC compared to MICT (p = 0.007) and to CON (p = 0.001). At the protein level, HIIT increased PAK1 expression in GC compared to MICT and CON (by ∼17%), but the difference was not statistically significant (p = 0.3, p = 0.2, respectively). There were no significant differences in the Rac1 or PAK1 expression in SOL between the groups.Conclusion: Our results indicate that HIIT, but not MICT, decreases Rac1 and PAK1 mRNA expression and increases the protein expression of especially Rac1 but only in fast-type muscle. These exercise training findings may reveal new therapeutic targets to treat patients with metabolic diseases.
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| 2. |
- Latva-Rasku, Aino, et al.
(författare)
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The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity : A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients.
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:5, s. 931-937
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS: This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA1c 6.5-10.5% (48-91 mmol/mol) and ≥3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were randomized 1:1 to receive 10 mg dapagliflozin or placebo daily for 8 weeks. Before and after the intervention, tissue insulin sensitivity was measured using [18F]-fluorodeoxyglucose and positron emission tomography during hyperinsulinemic-euglycemic clamp. Liver proton density fat fraction (PDFF) and adipose tissue volumes were assessed using MRI, and blood biomarkers were analyzed.RESULTS: After 8 weeks, glycemic control was improved by dapagliflozin (placebo-corrected change in HbA1c -0.39%, P < 0.01), but whole-body glucose uptake was not increased (P = 0.90). Tissue-specific insulin-stimulated glucose uptake did not change in skeletal muscle, liver, myocardium, or white and brown adipose tissue, and endogenous glucose production remained unaffected. However, there were significant placebo-corrected decreases in liver PDFF (-3.74%, P < 0.01), liver volume (-0.10 L, P < 0.05), visceral adipose tissue volume (-0.35 L, P < 0.01), interleukin-6 (-1.87 pg/mL, P < 0.05), and N-terminal prohormone of brain natriuretic peptide (-96 ng/L, P = 0.03).CONCLUSIONS: In this study, 8 weeks of treatment with dapagliflozin reduced liver PDFF and the volume of visceral adipose tissue in obese patients with type 2 diabetes. Although glycemic control was improved, no effect on tissue-level insulin sensitivity was observed.
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| 3. |
- Rebelos, Eleni, et al.
(författare)
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Insulin resistance is associated with enhanced brain glucose uptake during euglycemic hyperinsulinemia : A large-scale PET cohort
- 2021
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Ingår i: Diabetes Care. - Arlington : American Diabetes Association Inc.. - 0149-5992 .- 1935-5548. ; 44:3, s. 788-794
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of study participants across a wide range of age and insulin sensitivity. RESEARCH DESIGN AND METHODS [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 participants scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex,Mvalue from the clamp, steady-state insulin and free fatty acid levels, C-reactive protein levels, HbA1c, and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling. RESULTS Insulin sensitivity, indexed by theMvalue, was associated negatively with BGU in all brain regions, confirming that in insulin-resistant participants BGU was enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with additional increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein and free fatty acid levels, sex, and HbA1c were not associated with BGU. CONCLUSIONS In this large cohort of participants of either sex across a wide range of age and insulin sensitivity, insulin sensitivity was the best predictor of BGU. © 2021 by the American Diabetes Association.
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