Freddy Goldberg Eliaschewitz

Beneficial effects of prolactin and laminin on human pancreatic islet-cell cultures.

The problem of pancreas donor shortage could be addressed through in vitro islet-cell proliferation prior to transplantation into diabetic patients. Therefore, we set out to evaluate the effects of prolactin (rhPRL) and laminin on primary cultures of human pancreatic islets. Our results showed that rhPRL induced an increase in islet-cell number and in cumulative insulin secretion (p<0.01). However, glucose-induced insulin secretion was enhanced only in the presence of both laminin and rhPRL. In addition, we describe, for the first time in human islets, the PRL-induced activation of JAK2, and signal transducer and activator of transcription (STAT) 1, 3 and 5. Our results demonstrate a significant beneficial effect of rhPRL and laminin on human islets and support widely held notion that the closer physiological stimuli and environment of beta cells are mimicked, the better are the results in cell proliferation and secretory function, both essential for successful islet transplantation.

Microencapsulation and tissue engineering as an alternative treatment of diabetes

In the 70s, pancreatic islet transplantation arose as an attractive alternative to restore normoglycemia; however, the scarcity of donors and difficulties with allotransplants, even under immunosuppressive treatment, greatly hampered the use of this alternative. Several materials and devices have been developed to circumvent the problem of islet rejection by the recipient, but, so far, none has proved to be totally effective. A major barrier to transpose is the highly organized islet architecture and its physical and chemical setting in the pancreatic parenchyma. In order to tackle this problem, we assembled a multidisciplinary team that has been working towards setting up the Human Pancreatic Islets Unit at the Chemistry Institute of the University of São Paulo, to collect and process pancreas from human donors, upon consent, in order to produce purified, viable and functional islets to be used in transplants. Collaboration with the private enterprise has allowed access to the latest developed biomaterials for islet encapsulation and immunoisolation. Reasoning that the natural islet microenvironment should be mimicked for optimum viability and function, we set out to isolate extracellular matrix components from human pancreas, not only for analytical purposes, but also to be used as supplementary components of encapsulating materials. A protocol was designed to routinely culture different pancreatic tissues (islets, parenchyma and ducts) in the presence of several pancreatic extracellular matrix components and peptide growth factors to enrich the beta cell population in vitro before transplantation into patients. In addition to representing a therapeutic promise, this initiative is an example of productive partnership between the medical and scientific sectors of the university and private enterprises.

Type 2 diabetes in Brazil: epidemiology and management

Type 2 diabetes mellitus (T2DM) is one of the most important epidemic diseases in the world this century, and accounts for 90% of cases of diabetes globally. Brazil is one of the most important examples of the alarming picture of T2DM in emergent societies, being the country with the fourth largest number of people with diabetes. The aim of this paper is to review the literature on diabetes in Brazil, specifically looking at the epidemiology and management of T2DM. A literature search was conducted using PubMed and LILACS to identify articles containing information on diabetes in Brazil. Official documents from the Brazilian government, World Health Organization, and International Diabetes Federation were also reviewed.

Prolactin-induced changes in protein expression in human pancreatic islets.

Ex vivo islet cell culture prior to transplantation appears as an attractive alternative for treatment of type 1 diabetes. Previous results from our laboratory have demonstrated beneficial effects of human prolactin (rhPRL) treatment on human islet primary cultures. In order to probe into the molecular events involved in the intracellular action of rhPRL in these cells, we set out to identify proteins with altered expression levels upon rhPRL cell treatment, using two-dimensional (2D) gel electrophoresis and mass spectrometry (MS). An average of 300 different protein spots were detected, 14 of which were modified upon rhPRL treatment (p<0.01), of which 12 were successfully identified using MS and grouped according to their biological functions. In conclusion, our study provides, for the first time, information about proteins that could be critically involved in PRLs action on human pancreatic islets, and facilitate identification of new and specific targets involved in islet cell function and proliferation.

Glucose Control in Acute Myocardial Infarction: A Pilot Randomized Study Controlled by Continuous Glucose Monitoring System Comparing the Use of Insulin Glargine with Standard of Care

BACKGROUND This pilot study aimed to verify if glycemic control can be achieved in type 2 diabetes patients after acute myocardial infarction (AMI), using insulin glargine (iGlar) associated with regular insulin (iReg), compared with the standard intensive care unit protocol, which uses continuous insulin intravenous delivery followed by NPH insulin and iReg (St. Care). PATIENTS AND METHODS Patients (n=20) within 24 h of AMI were randomized to iGlar or St. Care. Therapy was guided exclusively by capillary blood glucose (CBG), but glucometric parameters were also analyzed by blinded continuous glucose monitoring system (CGMS). RESULTS Mean glycemia was 141±39 mg/dL for St. Care and 132±42 mg/dL for iGlar by CBG or 138±35 mg/dL for St. Care and 129±34 mg/dL for iGlar by CGMS. Percentage of time in range (80-180 mg/dL) by CGMS was 73±18% for iGlar and 77±11% for St. Care. No severe hypoglycemia (≤40 mg/dL) was detected by CBG, but CGMS indicated 11 (St. Care) and seven (iGlar) excursions in four subjects from each group, mostly in sulfonylurea users (six of eight patients). CONCLUSIONS This pilot study suggests that equivalent glycemic control without increase in severe hyperglycemia may be achieved using iGlar with background iReg. Data outputs were controlled by both CBG and CGMS measurements in a real-life setting to ensure reliability. Based on CGMS measurements, there were significant numbers of glycemic excursions outside of the target range. However, this was not detected by CBG. In addition, the data indicate that previous use of sulfonylurea may be a potential major risk factor for severe hypoglycemia irrespective of the type of insulin treatment.

Transplante de ilhotas na prática clínica: estado atual e perspectivas

Islet transplant is an innovative treatment for type 1 diabetic patients, which still lies between experimental and approved transplant therapy. Islet cells are seeded in a non-physiological territory where an uncertain fraction will be able to adapt and survive. Thus, the challenge lies in improving the whole procedure, employing the tools of cell biology, immunology and laboratory techniques, in order to reach the results obtained with whole organ transplant. This review describes the procedure, its progress to the present methodology and clinical results obtained. Future perspectives of islet transplantation in the light of recent biotechnological advances are also focused.

Islet vs. pancreas transplantation in Brazil: Defining criteria for pancreas allocation decision

Background: Many studies have evaluated whether there are characteristics related to pancreas donors and the islet isolation process that can influence in pancreatic islet yield. However, this analysis has not yet been performed in Brazil, one of the world leaders in whole pancreas organ transplantation (WOPT), where pancreas allocation for pancreatic islet transplantation (PIT) has no officially defined criteria. Definition of parameters that would predict the outcome of islet isolation from local pancreas donors would be useful for defining allocation priority in Brazil. Objective: To analyze the relationship between multiple donor-related and islet isolation variables with the total number of isolated pancreatic islet equivalents (IEQ) in a Brazilian sample of pancreas donors. Methods: Several variables were analyzed in 74 pancreata relative to the outcome of total IEQs obtained at the end of the process. Results: In univariate analysis, body mass index (BMI) (p = 0.003), the presence of fatty infiltrates in the pancreas as observed during harvesting (p = 0.042) and pancreas digestion time (p = 0.046) were identified as variables related to a greater IEQ yield. In a multivariate analysis a statistically significant contribution to the variability of islet yield was found only for the BMI (p = 0.017). A ROC curve defined a BMI = 30 as a cut-off point, with pancreata from donors with BMI > 30 yielding more islets than donors with BMI < 30 (p < 0.001). Conclusion: These data reinforces the importance of the donor BMI as a defining parameter for successful islet isolation and establishes this variable as a potential pancreas allocation criterion in Brazil, where there is an unequal competition for good quality organs between WOPT and PIT.