Embryonic stem (ES) cells display the ability to differentiate in vitro into a variety of cell lineages. Using a cell-trapping system, we have obtained an insulin-secreting cell clone from undifferentiated ES cells. The construction used allows the expression of a neomycin selection system under the control of the regulatory regions of the human insulin gene. The chimeric gene also contained a hygromycin resistance gene (pGK-hygro) to select transfected cells. A resulting clone (IB/3x-99) containing 16.5 ng/microg protein of total insulin displays regulated hormone secretion in vitro in the presence of various secretagogues. Clusters obtained from this clone were implanted (1 x 10(6) cells) in the spleen of streptozotocin-induced diabetic animals. Transplanted animals correct hyperglycemia within 1 week and restore body weight in 4 weeks. Whereas an intraperitoneal glucose tolerance test showed a slower recovery in transplanted versus control mice, blood glucose normalization after a challenge meal was similar. This approach opens new possibilities for tissue transplantation in the treatment of type 1 and type 2 diabetes and offers an alternative to gene therapy.

A healthy diet together with physical activity could induce weight loss and control the progression of non‐alcoholic fatty liver disease (NAFLD). However, the composition of diet has not been clearly established. Macronutrients such as saturated fatty acids (SFA), trans‐fats, simple sugars and animal proteins have a harmful effect on the liver. On the other hand, monounsaturated fats (MUFAs), polyunsaturated (PUFAs) omega‐3‐fats, plant‐based proteins and dietary fibres are considered to be beneficial to the liver. The impact of specific micronutrients is less well‐known. Nutrients are part of the food we eat. Food makes up our meals, which compose our dietary patterns. Non‐alcoholic fatty liver disease patients usually follow Western diets which are rich in soda, frozen junk food, juice, red meat, lard, processed meats, whole fat dairy foods, fatty snack foods, take‐away foods, cakes and biscuits and poor in cereals, whole grains, fruit, vegetables, extra virgin olive oil (EVOO) and fish. On the other hand, the Mediterranean diet (MD) is beneficial for NAFLD even when it is iso‐caloric or there are no changes in body weight. A new approach, called ‘nutritional geometry’ considers the importance of integrating nutrition, animals and the environment. The goal of this approach is to combine nutrients and foods in a model to understand how food components interact to regulate the properties of diets affecting health and disease. The use of algorithms developed by artificial intelligence (AI) to create a personalized diet for patients can provide customized nutritional counselling to prevent and treat NAFLD.

Cell signals produced during pancreas embryogenesis regulate pancreatic differentiation. We show that the developing pancreas releases soluble factors responsible for in vitro endocrine pancreatic differentiation from embryonic stem cells (ESCs). A mouse D3 ESC line was transfected with a human insulin promoter/βgeo/phosphoglycerate kinase–hygromycin-resistant construct. To direct differentiation, cells were cultured for 7 days to form embryoid bodies and then plated for an additional 7 days. During this 14-day period, besides eliminating leukemia inhibitory factor, cells were cultured in low serum concentration with the addition of conditioned media from embryonic day–16.5 pancreatic buds. Islet cell differentiation was studied by the following: (a) X-gal staining after neomycin selection, (b) BrdU (bro-modeoxyuridine) studies, (c) simple and double immunohistochemistry for insulin, C-peptide, and glucose transporter 2 (Glut-2), (d) reverse transcription–polymerase chain reaction for insulin and pancreas duodenum homeobox 1 (PDX-1), (e) insulin and C-peptide content and secretion assays, (f) intraperitoneal glucose tolerance test, (g) electrophysiology (patch-clamp studies in inside-out configuration), and (h) transplantation of differentiated cells under the kidney capsule of streptozotocin-diabetic mice. The differentiated ESCs showed the following: changes in the mRNA levels of insulin and PDX-1; coexpression of insulin, C-peptide, and Glut-2; glucose and tolbutamide-dependent insulin and C-peptide release; K-channel activity regulated by ATP; and normalization of blood glucose levels after transplantation into diabetic mice and hyperglycemia after graft removal. In this study, we establish a battery of techniques that could be used together to properly characterize islet cell differentiation. Moreover, identification of factors released by the developing pancreas may be instrumental in engineering β cells from stem cells.

Diabetes mellitus (DM) is considered a global pandemic, and the incidence of DM continues to grow worldwide. Nutrients and dietary patterns are central issues in the prevention, development and treatment of this disease. The pathogenesis of DM is not completely understood, but nutrient-gene interactions at different levels, genetic predisposition and dietary factors appear to be involved. Nutritional genomics studies generally focus on dietary patterns according to genetic variations, the role of gene-nutrient interactions, gene-diet-phenotype interactions and epigenetic modifications caused by nutrients; these studies will facilitate an understanding of the early molecular events that occur in DM and will contribute to the identification of better biomarkers and diagnostics tools. In particular, this approach will help to develop tailored diets that maximize the use of nutrients and other functional ingredients present in food, which will aid in the prevention and delay of DM and its complications. This review discusses the current state of nutrigenetics, nutrigenomics and epigenomics research on DM. Here, we provide an overview of the role of gene variants and nutrient interactions, the importance of nutrients and dietary patterns on gene expression, how epigenetic changes and micro RNAs (miRNAs) can alter cellular signaling in response to nutrients and the dietary interventions that may help to prevent the onset of DM.