Project: Helminth-derived glycoproteins and insulin sensitivity: from immunomodulatory properties to direct regulation of metabolic tissues

HelP-T2D (Helminth Products for Type 2 Diabetes).
Obesity, insulin resistance and type 2 diabetes (T2D) are rising at an alarming rate affecting almost 400 million people worldwide and expected to rise to 600 million by 2035. Although pharmacological treatments are currently available for T2D and its associated metabolic disorders, new innovative strategies are still needed for providing alternatives to progressive drug resistance to conventional medicines. Recent landmark studies have shown that type-2 immune responses are associated with improved insulin sensitivity and glucose homeostasis.

This is supported by the ability of parasitic helminths, the strongest natural stimuli of type-2 responses, to improve insulin sensitivity and glucose homeostasis in rodent models of insulin resistance. Over the past year, it has been  shown that helminth-derived molecules can also improve insulin sensitivity, which indicates that the beneficial effects of helminths on whole-body metabolic homeostasis is mediated by their intrinsic (immuno)modulatory properties rather than “parasitism” on caloric intake. Interestingly, helminth soluble egg antigens (SEA) and a structurally related synthetic polyvalent LeX glycoconjugate, were recently shown to improve glucose tolerance and insulin sensitivity in obese mice not only by immune-dependent mechanisms but also by directly modulating lipid metabolism in hepatocytes. Taken together, these data indicate that helminth products, notably highly glycosylated proteins, might constitute a source of unique molecules for manipulating metabolic processes, either by triggering tissue-specific Th2 immune responses and/or by directly targeting metabolic cells via glycan-mediated interaction with specific receptors.HelP-T2D constitutes a collaborative interdisciplinary pre-clinical project at the interface between immunology/glycobiology and metabolism. Our ultimate goal is to identify metabolically active glycoproteins and/or cellular targets that can ultimately lead to future therapeutic opportunities for the treatment of type 2 diabetes and associated metabolic disorders in humans.