Fruit fly as a model to study Diabetes by addressing the insulin-like query

Apparently, we started discussion with respect to culturing fruitfly the Six times Nobel prize winner!

Well, @Smiti came up with a approach about fruitfly as a model organism to study Diabetes.

Her objective was to find Drosophila melanogaster in her surroundings of Bandra, Mumbai
:arrow_right: @Smiti was telling about the experimental design she followed to culture fruitfly which she started long back on 8th October 2021.
Her objective was to find Drosophila melanogaster in her surroundings of Bandra, Mumbai
:arrow_right: @Smiti started trapping fruitflies in her surroundings and got a mixed culture of trapped fruitflies.
:arrow_right: After trapping she started making single line culture i.e started transferring gravid pregnant fruitfly into new culture bottles.
:arrow_right: Five bottles were setup for single line culture named SLBM A, B, C, D and E
SLBM - Single Line Bandra Mumbai
:arrow_right: Later smiti did identification of fruitfly to get a Drosophila melanogaster by looking at characteristics such as red eyes, brownish yellow thorax, and transparent pair of wings and further getting a Drosophila melanogaster in one of the bottle.

:arrow_right: @Smiti prepared five bottle setup in which SLBM A had 15 generations of fruitfly and were cultured for almost 4 months after which every two week she transferred flies to a new media bottle every 2 weeks.
:arrow_right: She made replicates and named it as SLBM A1 and kept on making replicates SLBM A1.1. and so on…
:arrow_right: After 15` generations all the flies were dead because of mites in the culture.

:arrow_right: In the B bottle she trapped female fly but not pregnant.
:arrow_right: In the C bottle she kept the cap open after transferring because of which the flies flew away.
:arrow_right: In the D bottle again there were mites forming and still the flies survived till 21` generation and she made four replicates. During exams she lost her culture.
:arrow_right: And the E bottle was took away by the rat.

@Smiti cultured the fruitflies in BRSV media i.e banana, rava, sugar and vinegar made at Homelab.

Moving on to the Diabetes part we come to know that fruitfly have seven insulin-like peptides and different insulin pathways and some are similar to humans as well which was known from a reference shared in ChatShaala.

The Drosophila insulin-like peptides (ILPs) also have nonredundant functions [1820]. The ILP2 peptide has the highest homology to the vertebrate insulin gene and is synthesized together with ILP1, ILP3, and ILP5 in the IPCs of the brain, and their synthesis depends on ILP3. ILP3 expression also activates the insulin pathway in the fat body [21]. ILP4, ILP5, and ILP6 are expressed in the midgut, ILp7 is expressed in the ventral nerve chord, and ILp2 is also expressed in the salivary glands and imaginal discs [22]. The Drosophila IPCs are the equivalent of the mammalian Langerhans’ islets ß pancreatic cells [23]. ILP6 is synthesized in the fat body and can partially substitute for ILP2 and ILP5. ILP2 loss-of-function mutations lead to an increase in lifespan, while loss in ILP6 causes reduced growth [23, 24].

From this reference we understand that Drosophila genome codes for seven several insulin-like peptides, and is secreted from specialized neurons (insulin-producing cells, or IPC) and glia in the brain and my assumption is that these seven different insulin-like gene copies have different functions.

As per the discussion on Context2Curriculum assumption made by @Abhi0703 was that the insulin-like genes will not be direct in their action thats why the cumulative effect of the proteins produced by insulin acts better whereas humans have only one gene because the humans might have gotten some some advantage in the process of evolution and hence that gene became very particular in action.
@Smiti thinks that insulin-like peptides plays a role in glucose metabolism. And they are with partially redundant functions and the insliun pathway is similar to humans, so does this partially redundant function means that these insulin-like peptides play a role in glucose metalbolism but there are some differences in insulin pathways with respect humans. Can these peptides come together to form one protein? And work as one single protein like insulin does in humans?
@rahulkushwaha says that it is named insulin-like on the basis of sequence structure and it might not be primarily function for different peptide in development, metabolism etc. They dont have to be the doing the same thing that they do in humans. Just because something is ‘insulin-lke’. Does all of them have to play a role in glucose metabolism? What do you think? @Smiti @KiranyadavR @Abhi0703 @jaikishan
Following on these, the redundant means anyone of the the seven genes can do the function if other six are inactivated but in partial redundancy the other six genes are not exactly same but partially similar as per @magpie
How does insulin act in human beings? What type of signaling, we are referring to, in the case of human insulin?
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/insulin-signaling
Here is an interesting take on the role of Insulin in Learning and Memory. Additionally, hippocampus, a critical brain area for learning and memory, is also an important target of insulin. Similar to peripheral tissues, insulin activates the IRS/PI3K/AKT pathway inducing the translocation of GSV to the plasma membrane. However, due to the higher expression of GLUT1 and GLUT3 in neuronal cells, the function of GLUT4 in the hippocampus remains to be determined. It has been suggested that the insulin-stimulated translocation of GSV contributes to a rapid fluctuation of glucose levels in the hippocampus that occurs during learning task (McNay, Fries, & Gold, 2000). Acute administration of physiological insulin concentration, enhances spatial working memory, via PI3K. When insulin signaling is blocked, in the hippocampus of rats, cognitive performance is impaired (McNay et al., 2010). In fact, insulin has been proposed as a regulatory factor of neuronal functions, not only by stimulating glucose uptake in the neurons, but also by modulating synaptic plasticity, neurotransmission and neurogenesis (Steculorum, Solas, & Brüning, 2014).

In Humans, Insulin, a hormone made by pancreas helps glucose from food get into the cells which provides energy for cell function. Sometimes body is not able to make insulin or enough insulin or is not used well. Glucose then stays in the blood and the level of blood glucose or blood sugar in the body increases which causes Diabetes.

Drosophila as a Model for Diabetes and Diseases of Insulin Resistance
P. Graham and L. Pick1

Drosophila melanogaster as a Model for Diabetes Type 2 Progression https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941822/ 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
The pancreas produces an exocrine secretion (pancreatic juice from the acinar cells) which then enters the duodenum through the main and accessory pancreatic ducts and endocrine secretions (glucagon and insulin from the pancreatic islets of Langerhans) that enter the blood Anatomy, Abdomen and Pelvis, Pancreas - StatPearls - NCBI Bookshelf Anatomy, Abdomen and Pelvis, Pancrea

3 Likes