Pairs of counter-regulatory hormones achieve very precise control of several plasma constituents. This precision implies integral control. Locally acting chromogranins and other statins within individual endocrine glands cause endocrine tissues to respond to the time integral of the error in the controlled variable, and not merely to the magnitude of that error. This produces integral control. Pairs of integral controllers need, however, to be linked to avoid homeostatic conflict. Thus the pancreatic islets consist of α-, and β-cells linked by gap junctions to form heterologous functional syncytial units. These probably act as flip-flop mechanisms which secrete either insulin or glucagon. Insulin is therefore always secreted at the expense of glucagon, and vice versa, allowing the two controllers to operate as an Integral Rein Control unit. When counterregulatory hormones are secreted by anatomically remote tissues then the co-secretion of a common inhibitory “link hormone” replaces the gaps junctions of the pancreatic islets. Co-secreted chromogranin A provides the link between the calcitonin-PTH pair, while somatostatin from the pancreas and hypothalamus allows growth hormone to operate in conjunction with insulin and glucagon without conflict.
Keywords: negative feed-back control, chromogranins, somatostatin, gaba, pancreastatin, parastatin, vasostatin, type 1 diabetes, type 2 diabetes
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