Dr. Ostrega studies how different proteins in the pancreas affect the production and release of insulin, a hormone that regulates blood sugar levels. By investigating proteins like calpain and Bcl-x(L), they explore why some individuals have difficulty producing insulin, particularly in the context of diabetes. Additionally, their research looks into how genetic variations can influence these mechanisms, thereby linking genetic predispositions to diabetes risk. The studies involve understanding how pancreatic cells respond to changes in blood sugar levels and how this might be altered in certain genetic conditions.
Key findings
Blocking calpain for 48 hours reduced insulin output by 40-80%, highlighting its critical role in insulin production and signaling.
Inhibiting calpain proteins led to higher insulin release in response to high blood sugar, indicating a key role in regulating insulin production and utilization in muscles and fat cells.
Mice with excess Bcl-x(L) protein could not effectively use glucose for energy, causing severe issues with blood sugar control despite protection against cell death.
In glucokinase mutant mice, exposure to high sugar levels enhanced their insulin secretion ability, contrasting with normal cells that worsened under the same conditions.
Mice deficient in the HNF-1alpha gene failed to secrete enough insulin despite having a normal number of insulin-producing cells, linking this gene to early-onset diabetes.
Frequently asked questions
Does Dr. Ostrega study diabetes?
Yes, Dr. Ostrega's research focuses on the mechanisms behind insulin production and secretion, particularly in relation to type 2 diabetes.
What treatments has Dr. Ostrega researched?
Dr. Ostrega's findings contribute to understanding potential treatments for diabetes by targeting proteins that regulate insulin secretion.
Is Dr. Ostrega's work relevant to patients with genetic forms of diabetes?
Absolutely, their research connects genetic variations with pancreatic dysfunction and insulin production issues, which are crucial for those with genetic forms of diabetes.
What are calpains and why are they important in Dr. Ostrega's research?
Calpains are proteins that play a role in cellular functions, including insulin secretion. Dr. Ostrega studies how these proteins affect insulin release and diabetes risk.
How do insulin-producing cells adapt to high blood sugar?
In their research, Dr. Ostrega found that some defective insulin-producing cells can adapt to high blood sugar levels by increasing their insulin secretion ability, while healthy cells may suffer.
Publications in plain English
Utilization of leukapheresis and CD4 positive selection in Treg isolation and the ex-vivo expansion for a clinical application in transplantation and autoimmune disorders.
2016
Oncotarget
Gołąb K, Grose R, Trzonkowski P, Wickrema A, Tibudan M +6 more
Plain English This study explored a new method for isolating and expanding T regulatory cells (Tregs), which are important for managing autoimmune diseases and helping organ transplants succeed. The researchers used a technique that involved filtering blood to acquire a higher number of Tregs, resulting in over 95% of these cells being high-quality and functional. This is significant because it shows that they can collect enough effective Tregs for clinical use, making potential treatments more viable.
Who this helps: This benefits patients with autoimmune disorders and those needing organ transplants.
Encapsulation of pancreatic islets within nano-thin functional polyethylene glycol coatings for enhanced insulin secretion.
2010
Tissue engineering. Part A
Kizilel S, Scavone A, Liu X, Nothias JM, Ostrega D +2 more
Plain English This study looked at a way to protect insulin-producing cells (islets) from being rejected when transplanted into diabetic patients. Researchers created a very thin coating for these islets using a special polymer, which helped them produce more insulin in response to sugar. The results showed that islets with this new coating released more insulin than untreated ones, highlighting a potential method to improve diabetes treatment by reducing the amount of tissue needed for effective transplants.
Who this helps: This benefits patients with insulin-dependent diabetes.
Islet isolation under cGMP conditions: replacing the coil.
2004
Transplantation proceedings
Garfinkel MR, Connors M, Ostrega D, Jarosz J, Philipson L +1 more
Plain English This study looked at improving the process of isolating islets (the insulin-producing cells from the pancreas) for transplantation by replacing a complicated metal coil with a disposable blood warming system. The researchers found that the new system warmed the islets to the needed temperature faster and just as effectively as the old coil, achieving 37 degrees Celsius in an average of 5.5 minutes. This is important because using a simpler, disposable system can make the islet isolation process cleaner and more compliant with health regulations.
Who this helps: This benefits patients needing islet transplants and the medical teams involved in their care.
Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency.
2003
The Journal of clinical investigation
Jackson RS, Creemers JW, Farooqi IS, Raffin-Sanson ML, Varro A +17 more
Plain English This study looked at two cases of a rare condition called proprotein convertase 1 (PC1) deficiency, which affects hormone regulation and can lead to various health issues like obesity and severe diarrhea. The second case demonstrated serious digestive problems, whereas the first case had signs of intestinal dysfunction that were not initially recognized. The findings highlight that PC1 is important for normal small intestine function and that its absence can lead to significant health challenges.
Who this helps: This research benefits patients with PC1 deficiency and their healthcare providers by improving understanding of the condition and its effects.
A 48-hour exposure of pancreatic islets to calpain inhibitors impairs mitochondrial fuel metabolism and the exocytosis of insulin.
2003
Metabolism: clinical and experimental
Zhou YP, Sreenan S, Pan CY, Currie KP, Bindokas VP +10 more
Plain English Researchers blocked a protein called calpain in mouse pancreas cells and found that doing so for 48 hours reduced insulin secretion by 40-80%, apparently by damaging the cells' ability to process glucose for energy. This discovery matters because a genetic variation in the calpain gene is linked to type 2 diabetes risk, and this experiment shows a potential mechanism: if calpain doesn't work properly, the insulin-producing cells fail to do their job.
Plain English Researchers found that blocking calpain proteins—which are found throughout the body—causes pancreases to release more insulin in response to high blood sugar, and simultaneously makes muscles and fat cells less responsive to insulin's signals. Since genetic variations in the calpain-10 gene are linked to type 2 diabetes, these results suggest that calpains are a key control point for how much insulin the body makes and how well cells use it.
Overexpression of Bcl-x(L) in beta-cells prevents cell death but impairs mitochondrial signal for insulin secretion.
2000
American journal of physiology. Endocrinology and metabolism
Zhou YP, Pena JC, Roe MW, Mittal A, Levisetti M +9 more
Plain English Researchers created mice with extra copies of a protein called Bcl-x(L) in their pancreas to see if it would protect insulin-producing cells from dying. While the protein did prevent cell death as expected, mice with very high levels of the protein developed severe problems with blood sugar control because their pancreatic cells couldn't properly use glucose to generate the energy signal needed to release insulin. The underlying problem was that the extra protein disrupted how mitochondria (the cell's power plants) work, preventing them from processing glucose and creating the chemical signals that trigger insulin release.
Apoptosis in insulin-secreting cells. Evidence for the role of intracellular Ca2+ stores and arachidonic acid metabolism.
1998
The Journal of clinical investigation
Zhou YP, Teng D, Dralyuk F, Ostrega D, Roe MW +2 more
Plain English This study looked at how changes in calcium levels inside insulin-producing cells can lead to cell death, specifically in a cell line called MIN6. They found that using a compound called thapsigargin lowered cell survival and triggered cell death, showing that it depleted calcium stores inside the cells and activated certain metabolic pathways involving arachidonic acid. For example, around 70% of the cells were affected after treatment, highlighting the importance of these chemical processes in cell health.
Who this helps: This helps patients with diabetes by providing insights into how insulin-secreting cells can be protected or harmed.
Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor-1alpha-deficient mice.
1998
The Journal of biological chemistry
Dukes ID, Sreenan S, Roe MW, Levisetti M, Zhou YP +6 more
Plain English This study looked at mice without a specific gene (HNF-1alpha) that is important for insulin production. Researchers found that these mice had trouble releasing insulin when stimulated by sugars, leading to high blood sugar levels. However, when they used certain substances to bypass the problem, insulin secretion improved, indicating a potential way to address this type of diabetes.
Who this helps: Patients with maturity onset diabetes of the young type 3 and their doctors.
Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.
1998
The Journal of clinical investigation
Pontoglio M, Sreenan S, Roe M, Pugh W, Ostrega D +10 more
Plain English Researchers studied mice with broken copies of a gene called HNF-1alpha to understand why mutations in this gene cause a form of diabetes in humans. They found that mice completely lacking this gene developed high blood sugar because their pancreas couldn't release enough insulin in response to glucose or other signals, even though they had a normal number of insulin-producing cells. This discovery shows that HNF-1alpha is essential for keeping pancreatic cells able to sense blood sugar and release insulin properly, which explains why people who inherit mutations in this gene develop early-onset diabetes.
Adaptation to hyperglycemia enhances insulin secretion in glucokinase mutant mice.
1998
Diabetes
Sreenan SK, Cockburn BN, Baldwin AC, Ostrega DM, Levisetti M +5 more
Plain English Researchers studied pancreatic cells from mice with a broken glucokinase gene (a gene that helps detect blood sugar) to see if exposing them to high blood sugar would improve their ability to make insulin. They found that cells from mutant mice actually recovered function when exposed to high sugar levels—they produced more insulin and better detected blood sugar changes—while normal cells exposed to the same high sugar levels became damaged and stopped working properly.
This matters because it explains why people with glucokinase gene mutations don't develop severe diabetes: their pancreatic cells adapt to high blood sugar instead of breaking down, and it suggests that having only one working copy of this gene actually provides protection against the cell damage that normally happens when blood sugar stays too high.
A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.
1997
The Journal of clinical endocrinology and metabolism
Warren-Perry MG, Manley SE, Ostrega D, Polonsky K, Mussett S +2 more
Plain English This study looked at a 58-year-old man with type 2 diabetes who had unusually high levels of a precursor to insulin called proinsulin, with levels at 708 pmol/L, compared to the normal range of 3-16 pmol/L. Researchers found a specific genetic change (G1552C mutation) in the insulin gene that caused a problem in how his body processes insulin, but this mutation wasn't linked to diabetes since it was also present in one of his healthy daughters. This matters because understanding such mutations helps doctors identify potential causes of insulin-related issues and improve treatment options.
Who this helps: This helps patients with diabetes and their doctors.
Plain English This study looked at how certain enzyme activities in the pancreas change as rats age, gain weight, and develop diabetes. Researchers found that, in obese rats with diabetes (ZDF and ZF), a specific enzyme called hexokinase (HK) was significantly more active—about 1.9 times greater in ZDF and 1.7 times greater in ZF compared to healthy rats. This increase may help maintain high insulin levels but does not explain why these diabetic rats fail to respond to rising glucose levels, which is crucial for managing diabetes.
Who this helps: This research benefits doctors and researchers working to understand diabetes and develop better treatments.
Plain English This study looked at two forms of proinsulin, a precursor to insulin, in blood samples from people with normal blood sugar levels and those with a type of diabetes called non-insulin-dependent diabetes mellitus (NIDDM). The researchers found that both the traditional immunoradiometric assays (IRMA) and a more advanced method called high-performance liquid chromatography (HPLC) can effectively measure proinsulin, with the IRMA showing consistent results (with variation below 13%) across different test subjects. This is important because accurately measuring proinsulin levels can help diagnose and manage diabetes more effectively.
Who this helps: Patients with diabetes and their doctors.
Plain English The study looked at how insulin production changes in someone who developed insulin-dependent diabetes (IDDM) over 13 months. Researchers found that even when blood sugar levels were normal, insulin secretion was reduced, and over time, the ability of the body to secrete insulin in response to sugar decreased significantly. This matters because it shows that insulin production starts to decline before diabetes is diagnosed, which could help in early detection and management of the disease.
Who this helps: This helps patients at risk of diabetes and doctors looking to identify early signs of the disease.
Alterations in immunoreactive proinsulin and insulin clearance induced by weight loss in NIDDM.
1994
Diabetes
Polonsky KS, Gumbiner B, Ostrega D, Griver K, Tager H +1 more
Plain English This study looked at how weight loss affects insulin production and clearance in people with diabetes, specifically those with non-insulin-dependent diabetes (NIDDM). Researchers found that after losing at least 10% of their body weight, participants with diabetes had improved insulin clearance and responded better to glucose, whereas those without diabetes did not show these changes. For example, insulin clearance increased significantly in those with overt diabetes after weight loss. This is important because it suggests that losing weight can help improve insulin function in people with diabetes, potentially leading to better blood sugar control.
Who this helps: Patients with non-insulin-dependent diabetes and their doctors.
Plain English This study looked at how insulin is released in pulses by the pancreas of different types of rats, focusing on the role of glucose in this process. Researchers found that in healthy rats, insulin was released in shorter pulses (about every 7 minutes), while in diabetic Zucker rats, it happened much less frequently (about every 15 minutes). This is important because it shows that the way glucose influences insulin release is disrupted in diabetes, potentially leading to higher blood sugar levels.
Who this helps: This helps patients with diabetes by providing insights into how insulin regulation works and what might be going wrong in their bodies.
Plasma insulin, C-peptide, and proinsulin concentrations in obese and nonobese individuals with varying degrees of glucose tolerance.
1993
The Journal of clinical endocrinology and metabolism
Reaven GM, Chen YD, Hollenbeck CB, Sheu WH, Ostrega D +1 more
Plain English This study looked at levels of insulin, proinsulin, and C-peptide in people with different glucose tolerance statuses: normal, impaired, and diabetic. Researchers found that patients with impaired glucose tolerance had the highest true insulin levels throughout the day, while those with diabetes had the highest levels of proinsulin. Understanding these differences is important because they help clarify how insulin production works in different degrees of glucose tolerance, which can lead to better diabetes management and treatment strategies.
Who this helps: This helps patients and doctors manage and understand diabetes better.
Hypoglycemia due to surreptitious injection of insulin. Identification of insulin species by high-performance liquid chromatography.
1991
Diabetes care
Given BD, Ostrega DM, Polonsky KS, Baldwin D, Kelley RI +1 more
Plain English Researchers studied patients who had low blood sugar due to undisclosed insulin injections, specifically looking at the type of insulin present in their bodies. They found that in three out of four patients, animal insulin was detected in their blood using a technique called high-performance liquid chromatography (HPLC). This method can help doctors confirm cases of low blood sugar caused by intentionally injecting insulin, which is important for proper diagnosis and treatment.
Who this helps: This helps doctors in accurately diagnosing patients experiencing unexplained low blood sugar episodes.
Lack of effect of high-dose biosynthetic human C-peptide on pancreatic hormone release in normal subjects.
1990
Metabolism: clinical and experimental
Wojcikowski C, Blackman J, Ostrega D, Lewis G, Galloway J +2 more
Plain English This study looked at how high doses of a substance called biosynthetic human C-peptide affect the release of hormones from the pancreas when healthy people consume sugar. Researchers found that, even at high levels, C-peptide did not significantly change the amounts of important hormones like insulin and glucose in the blood, suggesting it does not impact how the pancreas responds to sugar intake. This matters because it shows that giving extra C-peptide does not improve insulin release in normal individuals, clarifying its effects on hormone regulation.
Who this helps: This information is useful for doctors and researchers studying diabetes and pancreatic function.
Ingestion of a mixed meal does not affect the metabolic clearance rate of biosynthetic human C-peptide.
1986
The Journal of clinical endocrinology and metabolism
Licinio-Paixao J, Polonsky KS, Given BD, Pugh W, Ostrega D +2 more
Plain English This study looked at whether eating a mixed meal affects how quickly the body clears a specific hormone called C-peptide, which is linked to insulin secretion. Researchers found that the clearance rate of C-peptide stayed the same before and after patients consumed a 530-calorie meal, with measurements showing it at 4.5 ml/kg per minute before and 4.3 ml/kg per minute after eating. This matters because it confirms that C-peptide is a reliable indicator for understanding insulin secretion in people, especially after meals.
Who this helps: This helps patients with diabetes and their doctors better monitor insulin levels.