A Potential Target for Preventing Insulin Dependence in Diabetes
Type 2 diabetes (T2D) plagues over 30 million Americans. The relationship between the body and the hormone insulin governs T2D. The primary function of insulin is to aid cells in absorbing glucose from the bloodstream. When the body digests food, sugar is broken down and released into the blood as glucose, which is then used by cells as a source of energy. Patients with T2D are characterized by diminished insulin secretion by beta cells in the pancreas or increased insulin resistance, which is when cells stop responding to insulin. When there is decreased insulin secretion and lower insulin-mediated glucose uptake in cells, blood glucose concentration can dramatically increase to dangerous levels, known as hyperglycemia. Complications involving hyperglycemia include blindness, cardiovascular diseases, and nerve damage.
Treatments for T2D typically push beta cells to increase insulin production; however, none have been proven to prevent beta cell failure. Loss of beta cell function drives T2D patients toward dependence on insulin, thus requiring expensive, daily insulin injections. In order to understand the processes that drive beta cell failure and pinpoint potential targets for treating and preventing T2D, a joint team from Harvard University and Cornell University investigated adipsin, a protein that promotes insulin secretion from beta cells. Using diabetic mice as a model for human diabetes, the researchers introduced beta cells with the DNA that encodes adipsin, allowing the cells to produce the protein at elevated levels for months. They found that increasing adipsin expression in pancreatic cells increased insulin production while also maintaining beta cell mass. On the other hand, diabetic mice not injected with adipsin were used for comparison, and they suffered from severe hyperglycemia, low insulin levels, and changes in the structure of the pancreatic cells. Furthermore, the team found that increasing adipsin expression in mice without diabetes resulted in no change in insulin levels, glucose levels, or weight. With these findings, the researchers believe that future drugs used to increase adipsin concentration should, in concept, be safe.
Treatments for T2D typically push beta cells to increase insulin production; however, none have been proven to prevent beta cell failure. Loss of beta cell function drives T2D patients toward dependence on insulin, thus requiring expensive, daily insulin injections. In order to understand the processes that drive beta cell failure and pinpoint potential targets for treating and preventing T2D, a joint team from Harvard University and Cornell University investigated adipsin, a protein that promotes insulin secretion from beta cells. Using diabetic mice as a model for human diabetes, the researchers introduced beta cells with the DNA that encodes adipsin, allowing the cells to produce the protein at elevated levels for months. They found that increasing adipsin expression in pancreatic cells increased insulin production while also maintaining beta cell mass. On the other hand, diabetic mice not injected with adipsin were used for comparison, and they suffered from severe hyperglycemia, low insulin levels, and changes in the structure of the pancreatic cells. Furthermore, the team found that increasing adipsin expression in mice without diabetes resulted in no change in insulin levels, glucose levels, or weight. With these findings, the researchers believe that future drugs used to increase adipsin concentration should, in concept, be safe.
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What remained uncertain is how adipsin affects beta cells at a molecular level. By applying information from previous studies and genetic sequencing technology on cells with increased adipsin production, the researchers identified two proteins: complement component 3 (C3) and dual specificity phosphatase 26 (DUSP26). When exposed to an active form of C3, beta cells increased their insulin secretion while simultaneously decreasing the levels of molecules that promote apoptosis, or programmed cell death. By contrast, DUSP26 expression increased the amount of apoptotic molecules. Inhibiting the DUSP26 in beta cells increased insulin production and prevented apoptosis. Altogether, adipsin’s beneficial effects can be tied to raising activated C3 levels and lowering DUSP26 expression, effectively treating diabetic beta cell failure and preventing insulin dependence.
While this study has given light to potential methods of protecting beta cells when treating T2D, more studies must be done to unravel the exact mechanisms of how each researched protein works. However, the good news is that scientists are now one step closer to alleviating dependence on extremely expensive insulin among diabetes patients. This study provides a stepping stone for future research to further investigate adipsin as an alternative treatment for T2D.
While this study has given light to potential methods of protecting beta cells when treating T2D, more studies must be done to unravel the exact mechanisms of how each researched protein works. However, the good news is that scientists are now one step closer to alleviating dependence on extremely expensive insulin among diabetes patients. This study provides a stepping stone for future research to further investigate adipsin as an alternative treatment for T2D.
Featured Image Source: Myriams-Fotos
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