Blood sugar regulation and liver glucose supply in emotion and exertion

Cannon (1915) described sugar as the transport form of carbohydrate and starch as the storage form.¹ In well-fed animals the liver holds abundant glycogen, which is changed and set free in the blood as sugar in times of need. He gave the ordinary blood level as 0.06 to 0.1 per cent. Once it rose toward 0.2 to 0.3 per cent, sugar passed the kidneys and could be found in the urine, so glycosuria could serve as evidence of raised blood sugar.² Loeb (1916) cited Claude Bernard and Vitzou on a build-up of liver glycogen during growth and moulting in higher Crustacea.⁷

Cannon reported evidence that emotional states raise blood sugar. He cited Hirsch and Reinbach (1914), who found a psychic hyperglycemia in dogs fastened to a table. In one dog blood sugar rose from 0.11 to 0.14 per cent, and in another from 0.09 to 0.16 per cent.³ He also cited Folin, Denis and Smillie on students tested around important examinations. Of thirty-three students who had no sugar beforehand, six had small but unmistakable traces of sugar in the urine passed right after the ordeal.⁴

Bayliss (1915) described pancreatic diabetes as a state in which glycogen vanishes from the liver. Blood glucose might reach 0.8 per cent, yet no glycogen was stored. He called the meaning of this great loss of glucose obscure. Tests of the power of the tissues to consume carbohydrate had not shown that the power was entirely wanting, although it seemed to be diminished, especially in the later stages.⁵ He reported Hedon's transfusion experiments (1913). These showed that the glycosuria was due to the absence of a hormone made by the normal pancreas. Joining the pancreatic vein of a normal dog to the jugular vein of a diabetic dog almost abolished the glycosuria. In a variant experiment, part of a normal pancreas was intercalated in the circulation of a diabetic dog. It had a similar effect only when the pancreatic venous blood was allowed to pass through the liver.⁶

Goel and Mehta (2013) modelled gap junctions between insulin-secreting islet cells as a learning-like adaptation. They set this against the classical view that diabetes results from gap junction dysfunction. In their theory, reduced coupling is an adaptive response that keeps insulin control over hyperglycemia.⁸ Martínez and colleagues (2020) reviewed mitochondrial changes in the islets of type 2 diabetes. They reported that deleting UCP-2 in mice raised islet ATP generation and insulin secretion and reduced hyperglycemia in ob/ob mice.⁹