Tag Archives: insulin

Double Nobel prize winner: Frederick Sanger – the father of genomics

T. V. Danylova1*, S. V. Komisarenko2

1National University of Life and Environmental Sciences of Ukraine, Kyiv;
*e-mail: danilova_tv@ukr.net,
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;

Received: 02 February 2021; Accepted: 23 April 2021

This paper aims to outline briefly the main stages of Frederick Sanger’s scientific activity – the only person to have won two Nobel Prizes in Chemistry (1958, 1980). His work on the structure of proteins, especially that of insulin, and the determination of base sequences in nucleic acids made an immense impact on the development of biochemistry and especially on the development of a new scientific field – molecular biology. His methods for determining the primary structure of proteins and nucleic acids helped biochemists and molecular biologists to determine the structure of many proteins and nucleic acids and laid the basis for genetic engineering.

Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes

T. S. Vatseba1*, L. K. Sokolova2, V. M. Pushkarev2,
O. I. Kovzun2, B. B. Guda2, V. V. Pushkarev2,
M. D. Tronko2, N. V. Skrypnyk1, L. M. Zaiats1

1Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine;
2SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv;
*e-mail: tamara.vatseba@gmail.com

Received: 17 April 2020; Accepted: 13 November 2020

Modern research shows that patients with diabetes mellitus have an increased risk of cancer. PI3K/Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes. The aim of this study was to determine the state of РІ3K/Akt/mTORC1/p70S6K signaling cascade activity in peripheral mononuclear blood cells (PBMC) of patients with type 2 diabetes (T2D) relatively to the insulin and insulin-like growth factor (IGF-1) concentrations in blood plasma. Enzyme-linked immunosorbent assay was used to examine the levels of insulin and IGF-1 in blood plasma as well as the content of phosphorylated forms of Akt (Ser473), PRAS40 (Thr246), and p70S6K (Thr389) in PMBC. It was shown that in the blood plasma of patients with T2D the levels of insulin and IGF-1 were increased. Phosphorylation and activation of Akt by the mTORC2 protein kinase complex was not observed. At the same time, the relative degree of phosphorylation of mTORC1 inhibitor, PRAS40, and its substrate, p70S6K, was higher in PMBC of T2D patients in comparison with control values. These data suggest that phosphoinositide-dependent protein kinase 1 (PDK1) and, possibly, mitogen-activated protein kinase (MAPK) could mediate the effects of IGF-1 on Akt activation under type 2 diabetes.

The contribution of Nobel prize laureates to research of the protein structure: J. Sumner, J. Northrop, W. Stanley, L. Pauling, F. Sanger, M. Perutz, J. Kendrew

V. M. Danilova, R. P. Vynogradova, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: valdan@biochem.kiev.ua

Received: 11 Match 2020; Accepted: 15 May 2020

The second half of the 20th century was marked by remarkable discoveries in the chemistry and biochemistry of proteins, in particular, in establishing the protein structure. James Sumner, John Northrop, and Wendell Stanley, the Nobel Laureates in chemistry in 1946, were the first to isolate individual enzymes and viruses in a pure crystalline form and prove their protein nature, thereby making an invaluable scientific contribution to the development of important biological disciplines such as biochemistry, enzymology, virology, and molecular biology. A significant contribution to understanding chemical bonding in the formation of the different levels of a protein structure was made by Linus Pauling – a prominent American scientist of the 20th century. He was awarded the Nobel Prize in Chemistry in 1954 “for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances”. Biochemists know him well as the author of the secondary structure of proteins – the α-helix and the β-sheet. Frederick Sanger, a two-time Nobel Prize winner (1958 and 1980), was the first among researchers who determined the primary amino acid sequence of a protein, for example, of two insulin polypeptide chains A and B. F. Sanger proved that the sequence nature of proteins’ structures is analogous to that of gene sequences in the DNA, and thus, the same principles may be applied. The difficult question of how a protein molecule is arranged in space was answered by the English biochemists Max F. Perutz and John C. Kendrew. They determined the three-dimensional structure of hemoglobin and myoglobin proteins by X-ray diffraction and were awarded the Nobel Prize in Chemistry in 1962 “for their studies of the structures of globular proteins”.

Development on knowledge of hormone biochemistry in the works of the Nobel prize laureates of the first half of the 20th century: F. G. Banting, John J. R. Macleod, H. O. Wieland, A. O. Windaus, A. F. Butenandt, L. Ružička, E.Kendall, P. Hench, T. Reichstein

R. P. Vynogradova, V. M. Danilova, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: valdan@biochem.kiev.ua

Received: 18 February 2019; Accepted: 14 March 2019

The first half of the 20th century was marked by significant scientific advances in the study of hormones and vitamins. Among the first resear­chers working with hormones were F. Banting and J. Macleod, who discovered and characterized the pancreatic hormone insulin. This discovery catalyzed advances in the understanding of the mechanisms regulating biochemical processes – a new topic in the field of biological chemistry. The next important stage in the development of knowledge on biologically active substances was the works of organic chemists G. Wieland, A. Windaus, A. Butenandt and L. Ružička. They almost simultaneously identified and characterized the chemical structures of bile acids, vitamin D as well as female and male sex hormones. They found that all of these compounds are of a steroid nature and identified cholesterol as the starting material for their synthesis in the body. The studies of highly-active substances of steroid nature were continued by E. Kendall, F. Hench and T. Reichstein. They synthesized and investigated the structure and biological effects of corticosteroids, the hormones produced in the adrenal cortex. They were first to develop a method for the commercial manufacturing of cortisone, a hormone which is widely used to treat inflammatory processes. Thus, in the first half of the 20th century, organic chemists gave biochemists knowledge on the structure of essential for the human body substances – steroid compounds.

Association of allele variants of receptor gene of androgens (by the number of CAG-repeats) with androgen dependent hormonal metabolic indices of the organism

V. V. Korpachev, S. V. Melnychenko, R. G. Lukashova

State Institution V. Р. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
e-mail: vitascovna@gmail.com

This review discusses up-to-date conceptions concerning an association of androgen receptor gene (AR) allele (by the number of CAG-repeats) variations with the change of the receptor activity in humans. Different contradictory experiment results concerning the AR function dependence on the number of CAG-repeats have been analyzed. The authors discuss this problem paying mostly their attention to the interrelation between the number of CAG-repeats  and indicators of glucose and lipid metabolism in males and females.