Date on Senior Honors Thesis

5-2024

Document Type

Senior Honors Thesis

Degree Name

B.S.

Department

Biology

Author's Keywords

Metformin; Drosophila; Metabolism; AMPK; Sleep patterns; Feeding behavior

Abstract

Dimethylbiguanide, also known as metformin, is the single most prescribed oral treatment for non-insulin dependent diabetes mellitus, or type 2 diabetes, in Western countries. The primary mechanism of action that metformin acts through is the activation of AMP kinase, an important regulator of energy homeostasis. While the anti-diabetic effects of metformin are well documented, its effects on feeding and sleeping behaviors are not well characterized. Using the model organism Drosophila melanogaster, the mean daily quantity of food consumed was measured and compared between groups treated with several dosages of metformin. Feeding interactions such as meal frequency and length were also measured using the Fly-to-Liquid-food Interaction Counter (FLIC). Finally, activity and sleep patterns were measured using the Drosophila Activity Monitor (DAM). It was found that metformin treatment significantly increased food intake and interaction in wild type flies, while also marginally disrupting normal sleep patterns. This result helps verify a direct connection between metformin treatment and the modification of cellular metabolism.

Lay Summary

Type 2 diabetes is characterized by the inability of the body to properly use insulin. When food is broken down into glucose (the primary sugar used by cells), it begins to accumulate in the blood, raising blood sugar. When this happens, the pancreas releases insulin, which acts as a signal to cells to take up the sugar and use it for energy. However, when blood sugar levels remain high for prolonged periods, tissue becomes less sensitive to insulin, and the sugar stays in the blood, resulting in serious health complications.

Metformin is a popular drug used to treat type 2 diabetes. Metformin primarily increases tissues’ sensitivity to insulin, decreasing the amount of sugar in the blood without changing the amount of insulin being produced. Metformin is able to do this by activating cellular signals that govern metabolism. While metformin’s anti-diabetic effects have been clinically proven, the signals activated by metformin lead to a vast array of effects that haven’t been comprehensively studied.

This thesis uses fruit flies, a common and convenient model organism for genetics and molecular biology research, to identify metformin’s effects on feeding and sleeping behaviors activated by the signals mentioned above. This was done by measuring the quantity of food eaten and minutes spent asleep each day. Here I found that metformin treatment increases food intake amount, body weight, and the number of “meals” eaten per day. I also found that metformin fragments sleep patterns, resulting in less efficient bouts of sleep.

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