Role of Macrophage in Type 2 Diabetes Mellitus: Macrophage Polarization a New Paradigm for Treatment of Type 2 Diabetes Mellitus

Abstract

Metabolic diseases such as type 2 diabetes mellitus are usually in association with meta-inflammation. β-cell failure is a marked feature observed in the pathogenesis of type 2 diabetes mellitus. Type 2 diabetes mellitus (T2DM) is a heterogeneous situation that is accompanied with not only defective insulin secretion but also peripheral insulin resistance. β-cells are the primary organ for insulin secretion hence, it is crucial to maintain a significant β-cell mass in response to a variety of changes. Insulin resistance is a chief cause of T2DM leading to increased free fatty acid (FFA) levels which in turn elevates β-cell mass and insulin secretion as a compensation for insulin insensitivity. Recently, it has been established that amplified numbers of innate immune cells, cytokines, and chemokines result in detrimental effects on islets in such chronic conditions. Macrophage migration inhibitory factor (MIF) is the lymphokine that results in the prevention of arbitrary migration of macrophages and assembles macrophages at inflammatory loci. Inflammation is known to trigger monocytes in differentiating into macrophages. Progress of complications associated with type 2 diabetes mellitus, as indicated through recent findings, is also dependent on the buildup of macrophages in tissues vulnerable to diabetic injury. The present article scientifically evaluates the present knowledge concerning the mechanisms of recruitment of monocyte and macrophage-mediated injury in complications associated with type 2 diabetes mellitus. It also gives a description of some of the established and experimental therapies that might bring about a reduction in these inflammatory complications. Recent discoveries in the field of drug delivery have facilitated phenotype-specific targeting of macrophages. In this review, it is highlighted that the pathophysiology of type 2 diabetes mellitus, how macrophage induces type 2 diabetes mellitus and potential therapeutics for type 2 diabetes mellitus via macrophage-specific delivery.

Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells

“…15,45,46 Recently, natural products have attracted scientists’ attention for their contribution to the limitation of macrophage inflammatory response in the intra-islets and pancreatic β-cell death to deliver the benefits for diabetes management. 44,47,48 In the present study, we first demonstrated that lycopene alleviates the disorders in glucose and lipid metabolism in HFD/STZ-induced diabetic mice. Secondly, lycopene treatment promotes the dynamic balance of M1/M2 macrophages in the islets of diabetic mice and in HG/PA-stimulated RAW264.7 cells.…”

CD146+ Endometrial-Derived Mesenchymal Stem/Stromal Cell Subpopulation Possesses Exosomal Secretomes with Strong Immunomodulatory miRNA Attributes

“…These types of investigations could provide a rationale for further testing of eMSC EXOs as a viable therapeutic modality to manufacture cell-free products for inflammatory conditions, including osteoarthritis and diabetes. Specifically, macrophage infiltration and pro-inflammatory activation has been associated with synovitis/fat pad fibrosis severity in the knee joints of osteoarthritis patients [ 40 , 41 ], as well as pancreatic islet viability/insulin secretion capacity in diabetes patients [ 42 , 43 ].…”

Synergistic Effect of a Flavonoid-Rich Cocoa–Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats

“…In our study, ZDF animals showed an increased number of macrophages primarily localized within the islets. Macrophages infiltrating diabetic islets express an M1-like pro-inflammatory phenotype, contributing to local overproduction of inflammatory cytokines and activation of the NF-κB signaling pathway, ultimately leading to beta-cell apoptosis and dysfunction [ 39 ]. Although metformin treatment did not reduce macrophage numbers, it did decrease their infiltration, thereby mitigating islet inflammation.…”