Drosophila melanogasteras a Model for Diabetes Type 2 Progression

Abstract

Drosophila melanogaster has been used as a very versatile and potent model in the past few years for studies in metabolism and metabolic disorders, including diabetes types 1 and 2. Drosophila insulin signaling, despite having seven insulin-like peptides with partially redundant functions, is very similar to the human insulin pathway and has served to study many different aspects of diabetes and the diabetic state. Yet, very few studies have addressed the chronic nature of diabetes, key for understanding the full-blown disease, which most studies normally explore. One of the advantages of having Drosophila mutant viable combinations at different levels of the insulin pathway, with significantly reduced insulin pathway signaling, is that the abnormal metabolic state can be studied from the onset of the life cycle and followed throughout. In this review, we look at the chronic nature of impaired insulin signaling. We also compare these results to the results gleaned from vertebrate model studies.

The role of type 2 Diabetes mellitus as a risk factor for Alzheimer's and Parkinson's diseases

“…Both chemicals are toxic analogues of glucose transported to cells via Glut 2 transporter. Both treatments lead to insulin-producing cells necrosis, but by different mechanisms (Álvarez-Rendón et al, 2018).…”

“…Scientific literature on alloxane as a diabetogenic agent is extensively revised (Carvalho et al, 2003). The site of its diabetogenic action is the beta cell of the pancreas, the binding of this substance being very fast, generating toxic free radicals, leading to cell death by necrosis (Álvarez-Rendón et al, 2018;Rohilla & Ali, 2012). STZ is synthesized by the yeast Streptomycetes achromogenes and was initially identified as antimicrobial, however, preclinical studies revealed that its administration in high doses caused the destruction of β-pancreatic cells (Delfino et al, 2002;Furman, 2015).…”

“…STZ is cleaved, generating free methylnitrosourea which induces DNA fragmentation and deterioration of necrotic cells. Although STZ can also have toxic effects on other organs, its effectiveness and side effects depend mainly on tissue-specific Glut 2 expression, animal age and nutritional status (Álvarez-Rendón et al, 2018).…”

Diet Composition Differentially Affects Insulin Pathway Compromised and Control Flies

“…Several studies have demonstrated a growing number of genes and particular alleles that affect the proclivity to develop diabetes mellitus type II in humans [6], clouding results undertaken using human subjects with varying genetic backgrounds, making comparisons between studies difficult. The same is true of most diabetic animal models where genetic homogeneity is not strictly enforced [7].…”

“…Since the initial characterization of the first viable mutant in the Drosophila insulin pathway more than twenty years ago [9], the fruit fly has become a favored organism for insulin studies [7]. The insulin pathway in flies is evolutionarily conserved and has been extensively characterized [7, 10].…”