Author
Johannes E. M. N. Klein
Other affiliations: University of Stuttgart, University of Lübeck, University of York ...read more
Bio: Johannes E. M. N. Klein is an academic researcher from University of Groningen. The author has contributed to research in topics: Chemistry & Insulin resistance. The author has an hindex of 33, co-authored 96 publications receiving 4021 citations. Previous affiliations of Johannes E. M. N. Klein include University of Stuttgart & University of Lübeck.
Topics: Chemistry, Insulin resistance, Insulin, Adipose tissue, Medicine
Papers published on a yearly basis
Papers
More filters
TL;DR: Evidence is presented for the relevance of bimetallic Pd(III) complexes to catalysis for Pd-catalyzed C-H bond functionalizations in PhI(OAc)(2).
Abstract: PhI(OAc)2 is a common oxidant for Pd-catalyzed C−H bond functionalizations. Mechanistic hypotheses since the 1960s have suggested a Pd(II)/Pd(IV) mechanism. Here we present evidence for the relevan...
415 citations
TL;DR: In this paper, transition-metal-catalysed and -mediated processes for the preparation of oxindoles from anilides through C(3)-C(3a) bond formation are described.
269 citations
TL;DR: It is reported that the bond rearrangements expressed by curly arrows can be directly observed in ab initio computations, as transformations of intrinsic bond orbitals (IBOs) along the reaction coordinate.
Abstract: The “curly arrow” of Robinson and Ingold is the primary tool for describing and rationalizing reaction mechanisms. Despite this approach’s ubiquity and stellar success, its physical basis has never been clarified and a direct connection to quantum chemistry has never been found. Here we report that the bond rearrangements expressed by curly arrows can be directly observed in ab initio computations, as transformations of intrinsic bond orbitals (IBOs) along the reaction coordinate. Our results clarify that curly arrows are rooted in physical reality—a notion which has been challenged before—and show how quantum chemistry can directly establish reaction mechanisms in intuitive terms and unprecedented detail.
247 citations
TL;DR: Findings indicate cross-talk between adrenergic and insulin signaling pathways isprotein kinase A-dependent and, at least in part, protein kinase C-dependent, and could play an important role in the pathogenesis of insulin resistance associated with sympathetic overactivity and regulation of brown fat metabolism.
234 citations
TL;DR: Reconstitution experiments suggest that the discrepancy between PI 3-kinase activity and Akt activity is at least in part due to the p85-dependent negative regulation of downstream signaling of PI 3 -kinase.
199 citations
Cited by
More filters
TL;DR: The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.
Abstract: Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...
5,470 citations
TL;DR: The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide, and tissues such as muscle, fat and liver become less responsive or resistant to insulin.
Abstract: The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.
4,935 citations
3,322 citations
TL;DR: Analysis of genomic and clinical outcome data from 218 prostate cancer tumors revealed that copy-number alterations robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score.
3,310 citations
TL;DR: In light of the recent advances in understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, the exciting therapeutic opportunities for targeting this pathway to treat these diseases are discussed.
Abstract: Phosphatidylinositol 3-kinases (PI3Ks) evolved from a single enzyme that regulates vesicle trafficking in unicellular eukaryotes into a family of enzymes that regulate cellular metabolism and growth in multicellular organisms. In this review, we examine how the PI3K pathway has evolved to control these fundamental processes, and how this pathway is in turn regulated by intricate feedback and crosstalk mechanisms. In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases.
2,935 citations