Targeted delivery of curcumin for treating type 2 diabetes

Abstract

Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control. Curcumin is an anti-oxidant and nuclear factor kappa-B inhibitor derived from turmeric. A number of studies have shown that dietary curcumin reduces inflammation and delays or prevents obesity-induced insulin resistance and associated complications, including atherosclerosis and immune mediate liver disease. Unfortunately dietary curcumin is poorly absorbed by the digestive system and undergoes glucuronidation and excretion rather than being released into the serum and systemically distributed. This confounds understanding of how dietary curcumin exerts its beneficial effects in type 2 diabetes and associated diseases. New improved methods of delivering curcumin are being developed including nanoparticles and lipid/liposome formulations that increase absorption and bioavailability of curcumin. Development and refinement of these technologies will enable cell-directed targeting of curcumin and improved therapeutic outcome.

Oral Supplementation with Non-Absorbable Antibiotics or Curcumin Attenuates Western Diet-Induced Atherosclerosis and Glucose Intolerance in LDLR−/− Mice – Role of Intestinal Permeability and Macrophage Activation

“…Dietary curcumin is poorly absorbed and undergoes glucuronidation and excretion limiting its release into the circulation. Consequently, significant efforts are currently being directed to the development of novel methods for systemic or targeted delivery of curcumin [33]. The data presented here demonstrate for the first time that curcumin exerts potent effects in reducing metabolic diseases such as diabetes and atherosclerosis by modulating the intestinal barrier function, precluding the need for effective absorption and systemic bioavailability.…”

Phytobioactive compound-based nanodelivery systems for the treatment of type 2 diabetes mellitus – current status

“…[128][129][130][131] However, it has low potential through oral delivery due to the low water solubility and stability in gastrointestinal environment. [132][133][134][135][136] Nanodelivery systems are an alternative approach that can improve the stability of those compounds with improved bioavailability of curcumin.…”

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

“…This class of drugs raises Hsp 70 and improves insulin signaling, preserves diabetic islet cells, and reduces diabetic neuropathy. ) Improves glycemia, insulin signaling, anti-inflammatory, mitochondria generation renal, and nerve protection; blocks weight gain to antipsychotic medications; ischemia protection; improves diabetic wound healing; reduces liver fat; improves dyslipidemia Geranylgeranylacetone (Kavanagh et al 2011) Improves glycemia, insulin signaling, anti-inflammatory Alpha-lipoic acid (Gupte et al 2009b) Improves glycemia, insulin signaling, anti-inflammatory Xenohormetic plant compounds (Hooper et al 2010)-curcumin (Sahin et al 2012;Maradana et al 2013), carvacrol (Cho et al 2012;Wieten et al 2010), resveratrol (Han et al 2012;Ito-Nagahata et al 2013), metformin (Tsuei and Martinus 2012), astaxanthine (Lee et al 2010;Yuan et al 2011), naringin (Sharma et al 2011), rhodiola (Wang et al 2012;Panossian et al 2009), capsaicin (Luo et al 2012;Joo et al 2010) Improves glycemia, insulin signaling, and anti-inflammatory; reduce fatty liver; improves exercise performance; reduces fatigue; preserves kidney function; reduces diabetes-related cancer risk; improves endothelial function; extends life span of nematode Hemeoxygenase inducers (Li et al 2008) Improves glycemia, insulin signaling, anti-inflammatory Hsp90 inhibitors (Lee et al 2013;Farmer et al 2012) Improves glycemia, insulin signaling, anti-inflammatory Chemical chaperones (Kars et al 2010;Raciti et al 2010) Improves glycemia, insulin signaling, anti-inflammatory GLP agonist (Cunha et al 2009) Protects islets cells Hsp27 (Dai et al 2009) and Hsp72 (Chung et al 2008) gene overexpression Improves glycemia, improves insulin signaling, reduces inflammatory cytokines, reduces body fat, preserves beta cells…”