Are There Animal Models For Diabetes 1

Animal models of type 1 diabetes (T1D) enable the study of mechanisms underlying its pathogenesis and the evolution of therapeutic interventions. 1 of the most widely used models of the disease is the spontaneous diabetic Wistar rat, unremarkably referred to as the BB rat, which was first described in 1974 then more extensively reported on in 1978 by Nakhooda and colleagues.

This grouping performed a longitudinal study of 51 weanlings from insulin-treated diabetic male and non-diabetic female parents with the specific aim of tracking the evolution from normoglycaemia to overt diabetes. In order to characterize the illness onset and early on development, they monitored daily nutrient and h2o intake, besides as trunk weight, and nerveless urine and blood samples. These samples were collected biweekly as diabetes was left untreated until the animals' condition mandated sacrifice, at which indicate the pancreas was removed for histological staining.

Changes in analysed parameters were referenced to the onset of overt diabetes, defined equally the starting time mean solar day of detected glycosuria. They found that 9 of 51 animals became overtly diabetic, but the time of onset varied considerably (forty–87 days), every bit did incidence betwixt litters (9–50%). They too noticed that the onset of glycosuria was accompanied past rapid weight loss. Concurrently, the researchers measured a sharp increase in plasma levels of glucose and glucagon, as well every bit a subtract in insulin levels, for all ix overtly diabetic animals. This dysregulation of glucose homeostasis was besides detected via significant increases in plasma complimentary fatty acid and total claret ketone concentrations.

Furthermore, oral glucose tolerance tests showed abnormal glycaemic responses in six of 9 rats compared with historic period-matched non-litter-mate controls. Finally, histological staining revealed that islets of select diabetic rats were smaller, less numerous and composed mostly of non β-cells; however, end-phase morphologies differed considerably.

One of the main take-home messages of this study was the recognition that disease onset and progression are rapid, occurring on the timescale of hours to days, simply also heterogeneous. Many other groups would use the BB rat model in the coming decades to study T1D, including in the context of genetics, environmental factors and autoimmunity.

This article would certainly non be complete without mentioning the non-obese diabetic (NOD) mouse model, which was first described by Makino and colleagues in 1980. Along with the BB rat, this mouse model has proven useful for preclinical T1D research and is associated with several advantages linked to its ameliorate-defined genome, greater availability of lab reagents and imaging tools, and lower maintenance costs.

The start NOD mouse was generated during routine convenance of CTS mice, and discovered owing to its abnormal polyuria and glycosuria, accompanied by rapid weight loss. Although this first mouse died inside i calendar month, the researchers were able to establish the NOD strain via selective convenance, specifically by using its offspring to generate viii mating pairs tested for spontaneous diabetes and reproductive ability — a huge effort that involved more than i,500 mice in total.

It is important to point out that, although other groups had previously generated hereditary diabetic mouse strains suitable for the study of maturity-onset diabetes or juvenile-onset diabetes induced by a virus or chemical, the NOD mouse was the first spontaneous not-obese diabetic strain.

Researchers tracked body weight and water intake, also equally urine volume, food consumption, plasma and urine glucose levels, and plasma cholesterol over fourth dimension, defining the onset of diabetes based on a commercial urine glucose test. Interestingly, they establish much higher incidence rates in females (80%) than in males (x%), the latter besides featuring later disease onset. Histological analyses revealed lymphocyte infiltration into pancreatic islets, also as a reduction in the number of β-cells and size of islets.

These two fauna models of T1D have advanced our understanding of affliction pathophysiology. Still, clinical translation of therapeutics has remained challenging, as curative success is dependent on treatment dose, timing and other parameters. Researchers in the field now hold that, although useful, these remain mere models and insights gained cannot be straight applied to humans. In fact, clinical trials have shown that numerous therapeutic interventions that were constructive in animals later proved ineffective for patients with diabetes. Much work has focused on this issue and more remains to be done for the development of bona fide models to guide translation and more accurately predict therapeutic outcomes in humans.

Source: https://www.nature.com/articles/d42859-021-00007-0

Posted by: donaldmarome.blogspot.com