Having recently completed a comprehensive review of diabetes, I have been both fascinated, by our current understanding of the complex biology underlying this disease, and horrified, by the extent to which this disease affects our society and its increase in prevalence. I intend, therefore, to share some of my findings, available in the biological literature, in a 7-part series of posts on this topic; this being my first.

Put simply, Diabetes Mellitus is the body’s inability to control blood sugar through excretion of the glucose-regulating hormone insulin, by the pancreas. Insulin is produced and exocytosed by β-cell populations within the pancreas and type I diabetes results from an immunological β-cell degradation, of unknown origin or causation. Conversely, type II diabetes is known to be inducible through dietary alterations and rarely develops early in life.

Diabetes current affects 6% of the UK population — more than 1 in 20 people — and is more prevalent across much of the western and developing worlds. It is estimated, based on current trends in diabetic incidence and diabetes-causing ailments such as obesity, that current targets of suppressing increases in worldwide prevalence of diabetes will be far missed. Meanwhile, fatality resulting from diabetes is also increasing. This means that both our ability to prevent and treat diabetes is unable to cope with rates of increasing occurrence. In 2018, the United Nations General Assembly met specifically to discuss this rise in non-communicable diseases and pledged “all necessary efforts” to curb this situations escalation.

Amazing new artificial pancreas technologies have now allowed for type I diabetes sufferers to live relatively normal lives, without having to worry about requiring insulin injection or reducing their glucose consumption. By both sensing glucose and excreting insulin, in response, these devices combine the use of highly technical biosensors and sophisticated algorithms to choose the dose and rate of injection in a more-or-less constant manner. Recent advances have attempted to utilise two hormones within a single artificial pancreas but clinical studies have shown little improvement in their performance, with respect to single hormone technologies. This indicates a technological impasse in our ability to progress in this field and a new challenge for the medical and natural sciences. Despite these efforts, the rise in insulin-resistance derived type II diabetes make their gains inconsequential to the statistical decline, although vital to the lives of type I diabetics.

As we have mentioned, the body’s insulin is produced by the pancreas. The pancreatic cells originate as duodenal precursor cells, in the organic region region linking the stomach to the small intestine. This is likely due to the pancreas’s evolutionarily precedent function as a secretor of digestive enzymes into the duodenum through a shared orifice with the bile duct. The differential expression of a gene known as pancreatic and duodenal homeobox 1 (PDX1), between pancreatic and duodenal cells, due to early environmental conditions then allows them to develop as biologically distinct. The alveolar glands of the pancreas produce and secrete digestive enzymes, whilst group of β-cells lying between these alveoli, termed islets, produce insulin which is extracted through the veinous system.

The pancreas performs this role in response to rises in the detection of blood glucose, whilst this glucose is then metabolised by other organs of the body, mainly muscle fibre and the liver, in response to insulin. In a functional system, this insulin sensation in muscular and hepatic tissues would lead to a reduction in blood glucose and, subsequently, a reduction in insulin exocytosis, closing the glucose response loop. This review will look at the roles and behaviours of the pancreas, liver, and muscle tissue in regulating blood glucose and begins to explore how these organs fail to do so.

(Stay tuned for the next instalment entitled “Reviewing Diabetes: 1. How insulin reduces blood glucose.” )