scholarly journals A structural overview of the zinc transporters in the cation diffusion facilitator family

2019 ◽  
Vol 75 (4) ◽  
pp. 357-367 ◽  
Author(s):  
Camila A. Cotrim ◽  
Russell J. Jarrott ◽  
Jennifer L. Martin ◽  
David Drew
Keyword(s):  
Metal Binding ◽  
Family Members ◽  
Zinc Homeostasis ◽  
Cation Diffusion ◽  
Intracellular Organelles ◽  
Membrane Bound ◽  
Cation Diffusion Facilitators ◽  
Soluble C

The cation diffusion facilitators (CDFs) are a family of membrane-bound proteins that maintain cellular homeostasis of essential metal ions. In humans, the zinc-transporter CDF family members (ZnTs) play important roles in zinc homeostasis. They do this by facilitating zinc efflux from the cytoplasm to the extracellular space across the plasma membrane or into intracellular organelles. Several ZnTs have been implicated in human health owing to their association with type 2 diabetes and neurodegenerative diseases. Although the structure determination of CDF family members is not trivial, recent advances in membrane-protein structural biology have resulted in two structures of bacterial YiiPs and several structures of their soluble C-terminal domains. These data reveal new insights into the molecular mechanism of ZnT proteins, suggesting a unique rocking-bundle mechanism that provides alternating access to the metal-binding site.

scholarly journals Inside the Insulin Secretory Granule

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 515
Author(s):  
Mark Germanos ◽  
Andy Gao ◽  
Matthew Taper ◽  
Belinda Yau ◽  
Melkam A. Kebede
Keyword(s):  
Secretory Granules ◽  
Β Cells ◽  
Β Cell ◽  
Proinsulin Processing ◽  
Membrane Bound ◽  
Golgi Network ◽  
Insulin Secretory Granule ◽  
Insulin Storage ◽  
Cellular Stimulation

The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with the plasma membrane upon cellular stimulation to release insulin. Insulin is synthesized in the endoplasmic reticulum (ER) as a biologically inactive precursor, proinsulin, along with several other proteins that will also become members of the insulin SG. Their coordinated synthesis enables synchronized transit through the ER and Golgi apparatus for congregation at the trans-Golgi network, the initiating site of SG biogenesis. Here, proinsulin and its constituents enter the SG where conditions are optimized for proinsulin processing into insulin and subsequent insulin storage. A healthy β-cell is continually generating SGs to supply insulin in vast excess to what is secreted. Conversely, in type 2 diabetes (T2D), the inability of failing β-cells to secrete may be due to the limited biosynthesis of new insulin. Factors that drive the formation and maturation of SGs and thus the production of insulin are therefore critical for systemic glucose control. Here, we detail the formative hours of the insulin SG from the luminal perspective. We do this by mapping the journey of individual members of the SG as they contribute to its genesis.

scholarly journals Renoprotective Effects of DPP-4 Inhibitors

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 246
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Hiroyuki Takahashi ◽  
Ryoko Motonaga ◽  
Makito Tanabe
Keyword(s):  
Diabetic Kidney Disease ◽  
Experimental Studies ◽  
Review Article ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Membrane Bound ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Dipeptidyl peptidase (DPP)-4 inhibitors are widely used in the treatment of patients with type 2 diabetes (T2D). DPP-4 inhibitors reduce glucose levels by inhibiting degradation of incretins. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. It has been shown that an increased renal DPP-4 activity is associated with the development of DKD. A series of clinical and experimental studies showed that DPP-4 inhibitors have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by anti-fibrotic, anti-inflammatory, and anti-oxidative stress properties. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying renoprotection by DPP-4 inhibitors under diabetic conditions.

SUMMARY OF CHROMATOGRAPHIC ANALYSIS METHODS OF ANTI DIABETIC GLIFLOZINS EMPAGLIFLOZIN, CANAGLIFLOZIN AND DAPAGLIFLOZIN

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (07) ◽  
pp. 80-83
Author(s):  
W. A Zaghary ◽  
S. Mowaka ◽  
M. S. Hendy ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Biological Samples ◽  
Chromatographic Analysis ◽  
Dosage Forms ◽  
Drug Control ◽  
Bioanalytical Assays

Sodium glucose co-transporter-2 (SGLT-2) inhibitors are relatively new developed effective oral anti-diabetic agents used in treatment of type 2 Diabetes Mellitus. They present either alone or in combination with other ant diabetic agents such as linagliptin, Saxagliptin and metformin. Therefore, the necessity to explore and compare the existing analytical and bioanalytical assays used for determination of such drugs either single or in combination is crucial. Many methods were reported in the literature for the bio-analysis and analysis of three novel gliflozins with applying the method on different dosage forms and different chemical and biological samples. Furthermore, this review offered an overview of different methods used for determination of every drug alone in a tabulated comparative way. Moreover, the present review emphasized the most common stability indicating assays to be of interest to the analysts in the area of drug control.

“CHANGES IN THE NERVOUS SYSTEM IN PATIENTS WITH DIABETES MELLITUS TYPE 2 WITH NEPHROPATHY AND PROGNOSTIC SIGNIFICANCE OF NEUROMARKERS OF BRAIN INJURY. LITERATURE REVIEW"

2021 ◽  
pp. 3-8
Author(s):  
Yu. Urmanova ◽  
A. Holikov
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Nervous System ◽  
Type 2 Diabetes Mellitus ◽  
Biochemical Markers ◽  
Prognostic Significance ◽  
Functional Changes ◽  
Neurospecific Proteins

THE PURPOSE OF THE STUDY is to carry out an analysis of the literature evaluating diabetic encephalopathy by determining neuromarkers. MATERIAL AND METHODS. In this article, the authors analyzed the literature on the role of neuromarkers in patients with type 2 diabetes mellitus undergoing program hemodialysis. RESEARCH RESULTS. Among biochemical markers, the determination of the level of neurospecific proteins is actively being investigated. The main part of them is autoantigens, entering the bloodstream, can cause the appearance of autoantibodies, which, when the blood-brain barrier is impaired, enter the brain from the blood vessel and cause morphological changes, destructive processes in neurons, as well as the development of nonspecific acute-phase reactions like edema or inflammation. Biomarker studies for the diagnosis of various brain lesions have been under way for more than 20 years, but at present no ideal biomarker has been found. Among biochemical markers, the determination of the level of neurospecific proteins is being actively studied. In patients with type 2 diabetes mellitus undergoing hemodialysis, this issue is also relevant in view of the frequent vascular cerebrovascular complications, but few studies have been conducted. CONCLUSIONS. All of the above emphasizes the need to identify the features of clinical and functional changes in the nervous system in patients with type 2 diabetes mellitus receiving program hemodialysis and to evaluate the prognostic value of neuromarkers in early detection of the degree of brain damage. 

Energy Method for Determining Dynamic Characteristics of Mechanisms

1949 ◽  
Vol 16 (3) ◽  
pp. 283-288
Author(s):  
B. E. Quinn
Keyword(s):  
Dynamic Characteristics ◽  
Energy Method ◽  
Mechanical Systems ◽  
Direct Approach ◽  
Graphical Methods ◽  
Applied Forces ◽  
Complex Mechanical Systems

Abstract Two types of problems are dealt with in the paper which are involved in the design of mechanisms required to have specified dynamic characteristics: (1) Determination of applied forces required to produce specified dynamic characteristics. (2) Determination of the dynamic characteristics which will result from the application of known forces. While graphical methods may be used in the solution of type (1) problems involving more or less complex mechanical systems, they do not afford a direct approach to type (2) problems. The energy method which will be outlined can be applied in either case, although this paper will be primarily concerned with the determination of the dynamic characteristics which result when a known force is applied to a given mechanism.

Sign in / Sign up

Export Citation Format

Share Document