Counterregulation to acute and recurrent hypoglycemia in rats

Blood glucose is essential for the body's energy supply, and therefore several mechanisms exist to regulate blood glucose levels. When glucose abounds in the blood, it is taken up into the tissues, stimulated by the hormone insulin. Insulin is thereby the most important mechanism to counteract high glucose levels. There are however multiple mechanisms to counteract low blood glucose levels (hypoglycemia), the most important being the hormones glucagon and adrenaline. Together with other mechanisms, this provides an effective counterregulation of low glucose levels. This is however not the case for diabetic patients. Diabetes is characterized by high glucose levels and must therefore be treated with glucose-lowering drugs, such as insulin. This leads occasionally to hypoglycemia, and diabetic patients are therefore very dependent on a well-functioning counterregulation. In addition it has been shown that recurrent hypoglycemia decreases the counterregulatory responses more and more, for unknown reasons. The aim of the studies in this thesis was to further investigate the mechanisms behind the counterregulatory responses to hypoglycemia. In addition it was investigated how and why these responses decrease with recurrent hypoglycemia. All studies were performed in rats. The most important finding is that the counterregulatory mechanisms are coordinated in a very intricate way, aiming to keep glucose levels above a certain minimum level. Furthermore it was shown that a certain neuronal pathway in the hypothalamus plays an essential role herein. Finally it was shown in a number of studies with recurrent hypoglycemia that rats also show a decrease in the counterregulatory responses.