Beta cell dysfunction and insulin resistance are inherently complex with their interrelation for triggering the pathogenesis of diabetes also somewhat undefined. Both pathogenic states induce hyperglycemia and therefore increase insulin demand. Beta cell dysfunction results from inadequate glucose sensing to stimulate insulin secretion therefore elevated glucose concentrations prevail. Persistently elevated glucose concentrations above the physiological range result in the manifestation of hyperglycemia. With systemic insulin resistance, insulin signaling within glucose recipient tissues is defective therefore hyperglycemia perseveres. Beta cell dysfunction supersedes insulin resistance in inducing diabetes. Both pathological states influence each other and presumably synergistically exacerbate diabetes. Preserving beta cell function and insulin signaling in beta cells and insulin signaling in the glucose recipient tissues will maintain glucose homeostasis.

Type 2 diabetes is primarily associated with insulin resistance and β-cell dysfunction. Maintenance of functional mature β-cells is imperative for ensuring glucose homeostasis. This can be achieved by optimal expression of key transcription factors that are required for normal pancreatic development and maintaining β-cell function. Defining the regulation of transcription factors as well as their regulation of important β-cell genes like insulin will provide further insight into elucidating the mechanisms leading to β-cell dysfunction.

Although pancreatic β-cells are capable of adapting their mass in response to insulin requirements, evidence has shown that a dietary insult could compromise this ability. Fetal malnutrition has been linked to low birth weight and the development of type 2 diabetes later in life, while reduced β-cell mass has been reported in adult rats fed a high-fat diet (HFD). Reported here are the effects of exposure to a HFD, during different periods of gestation, on neonatal rat weight and β- and α-cell development. The experimental groups were composed of neonatal offspring obtained from Wistar rats fed a high-fat (40% as energy) diet for either the first (HF1), second (HF2), or third (HF3) week, or all three (HF1–3) weeks of gestation. Neonatal weights and circulating glucose and insulin concentrations were measured on postnatal day 1, after which the pancreata were excised and processed for histological immunocytochemical examination and image analysis. HF1 and HF2 neonates were hypoglycemic, whereas HF1–3 neonates were hyperglycemic. Low birth weights were observed only in HF1 neonates. No significant differences were detected in the circulating insulin concentrations in the neonates, although β-cell volume and numbers were reduced in HF1–3 neonates. β-cell numbers also declined in HF1 and HF3 neonates. α-cell volume, number and size were, however, increased in HF1–3 neonates. α-cell size was also increased in HF1 and HF3 neonates. In neonates, exposure to a maternal HFD throughout gestation was found to have the most adverse effect on β-cell development and resulted in hyperglycemia.

Lineage tracing studies have revealed that transcription factors play a cardinal role in pancreatic development, differentiation and function. Three transitions define pancreatic organogenesis, differentiation and maturation. In the primary transition, when pancreatic organogenesis is initiated, there is active proliferation of pancreatic progenitor cells. During the secondary transition, defined by differentiation, there is growth, branching, differentiation and pancreatic cell lineage allocation. The tertiary transition is characterized by differentiated pancreatic cells that undergo further remodeling, including apoptosis, replication and neogenesis thereby establishing a mature organ. Transcription factors function at multiple levels and may regulate one another and auto-regulate. The interaction between extrinsic signals from non-pancreatic tissues and intrinsic transcription factors form a complex gene regulatory network ultimately culminating in the different cell lineages and tissue types in the developing pancreas. Mutations in these transcription factors clinically manifest as subtypes of diabetes mellitus. Current treatment for diabetes is not curative and thus, developmental biologists and stem cell researchers are utilizing knowledge of normal pancreatic development to explore novel therapeutic alternatives. This review summarizes current knowledge of transcription factors involved in pancreatic development and β-cell differentiation in rodents.

Diabetic nephropathy is a complex disease that involves increased production of free radicals which is a strong stimulus for the release of pro-inflammatory factors. We evaluated the renal protective effect of kolaviron (KV) - a Garcinia kola seed extract containing a mixture of 5 flavonoids, in diabetes-induced nephrotoxic rats. Male Wistar rats were divided into 4 groups: untreated controls (C); normal rats treated with kolaviron (C+KV); untreated diabetic rats (D); kolaviron treated diabetic rats (D+KV). A single intraperitoneal injection of streptozotocin (STZ, 50mg/kg) was used for the induction of diabetes. Renal function parameters were estimated in a clinical chemistry analyzer. Markers of oxidative stress in the kidney homogenate were analyzed in a Multiskan Spectrum plate reader and Bio-plex Promagnetic bead-based assays was used for the analysis of inflammatory markers. The effect of kolaviron on diabetes-induced apoptosis was assessed by TUNEL assay. In the diabetic rats, alterations in antioxidant defenses such as an increase in lipid peroxidation, glutathione peroxidase (GPX) activity and a decrease in catalase (CAT) activity, glutathione (GSH) levels and oxygen radical absorbance capacity (ORAC) were observed. There was no difference in superoxide dismutase (SOD) activity. Diabetes induction increased apoptotic cell death and the levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α with no effect on IL-10. Kolaviron treatment of diabetic rats restored the activities of antioxidant enzymes, reduced lipid peroxidation and increased ORAC and GSH concentration in renal tissues. Kolaviron treatment of diabetic rats also suppressed renal IL-1β. The beneficial effects of kolaviron on diabetes-induced kidney injury may be due to its inhibitory action on oxidative stress, IL-1β production and apoptosis.

Cardiovascular disease, cancer, diabetes, and chronic respiratory diseases, targeted by Sustainable Development Goal 3.4, afflict millions of people and account for the highest global morbidity and mortality. Obesity is associated with noncommunicable diseases. Globally, diets have become sweeter, saltier with higher fat content, whereas physical activity has declined; which triggers the onset of obesity and noncommunicable diseases. Healthy nutrition and regular exercise are the foundations for healthy living and important for preventing noncommunicable diseases, in alignment with health promotion. The preconception, gestational, and lactational periods present windows for improving and optimizing progeny growth and development for better health outcomes. Malnutrition is a major risk factor for noncommunicable diseases; therefore ingesting healthy nutritious food, over the life‐course, is critical for countering these global epidemics that have a more profound adverse impact on people from low‐ and middle‐income countries. To combat obesity and noncommunicable diseases, people's ownership of their health, government action, and private sector responsibility should be aligned and supported by global initiatives and enabled through partnerships and collaborations. Many noncommunicable diseases are avertable through health promotion strategies mainly directed at the maternal and child health lifecycle, by focusing on women of reproductive age (prior to and during pregnancy, and during lactation) and during infancy and childhood, adolescence, adulthood, and ageing. Healthy lifestyles support health promotion and disease prevention, which is cost‐effective for noncommunicable diseases. The global high burden of obesity and noncommunicable diseases remains a complex and prevalent challenge; therefore, the adoption of healthy lifestyles is critical to slow down their onset and exacerbation.