Polymeric carrier-mediated intracellular delivery of phosphatidylinositol-3,4,5-trisphosphate to overcome insulin resistance

Kachko, Ilana; Traitel, Tamar; Goldbart, Riki; Silbert, Liron; Katz, Marina; Bashan, Nava; Jelinek, Raz; Rudich, Assaf; Kost, Joseph

doi:10.3109/1061186x.2015.1052076

Cited by 4 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The outcomes of this experiment are similar to those of an earlier study employing PEI25 as a carrier for PIP3 [51]. Polyethyleneimine (PEI-25, 25 kDa) was previously identified as an effective vehicle for PIP3, forming complexes observed on the cell membrane within approximately one minute.…”

Section: Cellular Uptake Of the Q-starch/pip3 Complexessupporting

confidence: 83%

The Potential of PIP3 in Enhancing Wound Healing

Blitsman,

Hollander,

Benafsha

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Given the role of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in modulating cellular processes such as proliferation, survival, and migration, we hypothesized its potential as a novel therapeutic agent for wound closure enhancement. In this study, PIP3 was examined in its free form or as a complex with cationic starch (Q-starch) as a carrier. The intracellular bioactivity and localization of free PIP3 and the Q-starch/PIP3 complexes were examined. Our results present the capability of Q-starch to form complexes with PIP3, facilitate its cellular membrane internalization, and activate intracellular paths leading to enhanced wound healing. Both free PIP3 and Q-starch/PIP3 complexes enhanced monolayer gap closure in scratch assays and induced amplified collagen production within HaCAT and BJ fibroblast cells. Western blot presented enhanced AKT activation by free or complexed PIP3 in BJ fibroblasts in which endogenous PIP3 production was pharmacologically inhibited. Furthermore, both free PIP3 and Q-starch/PIP3 complexes expedited wound closure in mice, after single or daily dermal injections into the wound margins. Free PIP3 and the Q-starch/PIP3 complexes inherently activated the AKT signaling pathway, which is responsible for crucial wound healing processes such as migration; this was also observed in wound assays in mice. PIP3 was identified as a promising molecule for enhancing wound healing, and its ability to circumvent PI3K inhibition suggests possible implications for chronic wound healing.

show abstract

Section: Cellular Uptake Of the Q-starch/pip3 Complexessupporting

confidence: 83%

The Potential of PIP3 in Enhancing Wound Healing

Blitsman,

Hollander,

Benafsha

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mice with deficient PI3K subunit (heterozygous for p110α or p110β) displayed impaired glucose metabolism (Figure ) . In addition, exogenous PIP3 supplementation in L6 muscle cells increased both glucose uptake and glucose utilization and the effect was mediated by the activation of GLUT4 …”

Section: Experimental Evidence For the Association Between Phospholipmentioning

confidence: 99%

“…63,64 In addition, exogenous PIP3 supplementation in L6 muscle cells increased both glucose uptake and glucose utilization and the effect was mediated by the activation of GLUT4. 65 PIP2 also participates in the insulin secretion process. As plasma glucose rises, the ATP concentration increases and ADP concentration decreases, resulting in K(ATP) channel closure, membrane depolarization, Ca 2+ influx and insulin release ( Figure 3).…”

Section: The Role Of Phosphatidylinositol and Derivatives Of Phosphmentioning

confidence: 99%

The relationship between phospholipids and insulin resistance: From clinical to experimental studies

Chang

Hatch

Wang

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Insulin resistance induced by high‐fat diet and impropriate life style is a major contributor to the pathogenesis of metabolic disease. However, the underlying molecular mechanisms remain unclear. Recent studies in metabolic dysfunction have extended this beyond simply elevated cholesterol and triglycerides levels and have identified a key role for lipid metabolism. For example, altered phospholipid metabolism has now become central in the pathogenesis of metabolic disease. In this review, we discuss the association between insulin sensitivity and phospholipid metabolism and highlight the most significant discoveries generated over the last several decades. Finally, we summarize the current knowledge surrounding the molecular mechanisms related to phospholipids and insulin resistance and provide new insight for future research into their relationship.

show abstract

“…The researchers condensed polyethyleneimine (PEI) 25 kDa and PI(3,4,5)P3 into PEI-25/PIP3 nanoparticles whose cationic charge (derived from PEI25) caused PI(3,4,5)P3 to be retained at the cell perimeter. This strategy was thought to mimic the extent and cellular organization of PI(3,4,5)P3, which is preferable for insulin stimulation ( Kachko et al ., 2015 ).…”

Section: Glycerophospholipidsmentioning

confidence: 99%

Bioactive Lipids and Their Derivatives in Biomedical Applications

Park

Choi

Kim

et al. 2021

Biomolecules & Therapeutics

View full text Add to dashboard Cite

Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.

show abstract

Polymeric carrier-mediated intracellular delivery of phosphatidylinositol-3,4,5-trisphosphate to overcome insulin resistance

Cited by 4 publications

References 48 publications

The Potential of PIP3 in Enhancing Wound Healing

The Potential of PIP3 in Enhancing Wound Healing

The relationship between phospholipids and insulin resistance: From clinical to experimental studies

Bioactive Lipids and Their Derivatives in Biomedical Applications

Contact Info

Product

Resources

About