👤 Gustav Dallner

Chronic hyperglycemia inflicts serious cellular damage by inducing oxidative stress through the excessive production of free radicals. This oxidative milieu may impair the cellular redox capacity and disrupt the insulin-like growth factor (IGF) system, thereby increasing the risk of cardiovascular complications. This study aimed to investigate plasma levels of components of the IGF system and antioxidant biomarkers in young adults with type 1 diabetes mellitus (T1DM) compared to age-matched healthy controls in Brazil. This study included 129 patients with T1DM (76 female, 53 male; mean age 26.97 ± 0.6 years) and 95 healthy controls (61 female, 34 male; mean age 27.35 ± 0.68 years). Young Brazilian adults with T1DM had significantly lower mean IGF-I and higher mean IGFBP-1 levels compared to healthy controls. The T1DM group showed a more atherogenic profile, characterized by a significantly elevated ApoB/ApoA1 ratio and increased oxidized LDL levels. However, a subset of patients with significantly better glycemic control exhibited serum IGF-I and IGFBP-1 levels within the normal range observed in controls, which may indicate the presence of residual functional beta-cell activity or reflect better glycemic control in this subgroup. Antioxidant components and oxidative stress biomarkers were significantly upregulated in the T1DM group compared to the control group, suggesting a compensatory adaptive response. No significant correlation was observed between biomarkers of oxidative stress and the IGF-system. Show less

The organ content of the mevalonate pathway lipids was investigated in liver-X-receptor (LXR) α, β and double knock-out mice. An extensive or moderate increase of total cholesterol in the double KO mice was found in all organs elicited by the increase of the esterified form. In LXRα and double KO mice, coenzyme Q (CoQ) was decreased in liver and increased in spleen, thymus and lung, while dolichol was increased in all organs investigated. This effect was confirmed using LXR- agonist GW 3965. Analysis of CoQ distribution in organelles showed that the modifications are present in all cellular compartments and that the increase of the lipid in mitochondria was the result of a net increase of CoQ without changing the number of mitochondria. It appears that LXR influences not only cellular cholesterol homeostasis but also the metabolism of CoQ and dolichol, in an indirect manner. Show less

Uptake of dietary coenzyme Q (CoQ) into organs is limited but there are some exceptions such as adrenal glands and ovaries. Under deficient conditions an optimal solution could be stimulation of the endogenous synthesis. In rodent exercise, cold exposure and a few substances elevate the CoQ levels to some extent. Investigations of the nuclear receptors PPARalpha, RXRalpha and LXRalpha&beta did not answer the question which nuclear receptor regulates CoQ biosynthesis and at present we cannot design a ligand for upregulation of the synthesis. Upon ultraviolet irradiation of CoQ a number of products are formed which influence the synthesis of the mevalonate pathway lipids. Among them epoxidated derivatives were identified. Upon chemical epoxidation of a series of polyisoprenoids it was found that none of the tested poly-cis polyisoprenols had any effect but some of the all-trans polyisoprenols stimulated CoQ synthesis and in some cases also inhibited cholesterol biosynthesis. Tocotrienol epoxides were proved to be very efficient, those having one epoxide in the side chain doubled or trebled the CoQ synthesis while those with two epoxides additionally also inhibited cholesterol synthesis by 50-90%. The elevation of CoQ synthesis was elicited by increased mRNA levels for biosynthetic enzymes while the inhibition point in the cholesterol synthesis was localized to oxidosqualene cyclase. Show less