Mathematical modelling the systemic regulation of blood glucose: 'a top-down' systems biology approach.

The objective of this article is to review the mechanisms which the body uses to regulate its function. The author considers, in particular, the nature and structure of the physiological systems with a specific focus upon the systemic regulation of blood glucose and highlights an innovative technology, based upon the top-down cognitive approach, which incorporates a unique mathematical model of the physiological systems and autonomic nervous system. Most systems biology is a development of the prevailing reductionist biomedical paradigm. It adopts a bottom-up approach seeking systemic justification for biochemical and biophysical research findings. By contrast the 'top-down' approach considers the neural regulation of the physiological systems and the neurological, cognitive and biochemical consequences of systemic dysfunction i.e. the consequences of sensory input upon the neural regulation of the body's systems, organs, and its cellular and molecular biochemistry. In conclusion, the evidence suggests that the onset and progression of Diabetes Mellitus cannot be accurately assessed by individual biomedical indices but instead that the regulation of blood glucose is one of a number of inter-related physiological systems which act in a coordinated manner in order to maintain the body's physiological stability.

Diabetes mellitus decreases the expression of calcitonin-gene related peptide, gamma-amino butyric acid and glutamic acid decarboxylase in human pancreatic islet cells.

OBJECTIVES: The pattern of distribution of calcitonin-gene related peptide (CGRP), a neuropeptide, gamma-aminobutyric acid (GABA), a neurotransmitter and GABA-converting enzyme, glutamic acid decarboxylase (GAD) in the pancreas of diabetic patients was investigated to determine whether diabetes mellitus influences the expression of these biological transmitters. METHODS: Pancreatic tissue samples retrieved, during pancreatectomy, from cancer patients with and without Type 2 diabetes were paraffin embedded. The expression of CGRP, GABA and GAD was examined in pancreatic tissue using immunofluorescence techniques. RESULTS: CGRP, GABA and GAD were observed in many cells located in the central as well as the peripheral regions of pancreatic islet. The expression of CGRP, GABA and GAD decreased dramatically in pancreatic islet cells of diabetic patients compared to control. CGRP and GABA co-localized with glucagon in some pancreatic islet cells of both normal and diabetic patients. The pattern of distribution of CGRP, GABA and GAD in normal and Type 2 diabetic patients was similar to that of insulin. CONCLUSION: The number of human pancreatic islet cells expressing CGRP, GABA and GAD decreased significantly after the onset of Type 2 diabetes. These neuropeptides and neurotransmitters may play a role in the regulation of pancreatic beta cell function.