Archives for April 2011

Comments to Lee et al: Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice.

Diabetes 60:391-397, 2011.

Accumulating evidence during the last several decades has suggested that glucagon is of key importance for diabetes hyperglycemia. Thus, patients with type 2 diabetes have hyperglucagonemia and increased hepatic glucose output, and the hyperglycemia seems to be caused by a defective suppression of glucagon during hyperglycemia (1). A recent experimental study by Lee and collaborators examined the role of glucagon in mice with type 1 diabetes induced by streptozotin (2). They approached this aim by using a mouse model with genetic deletion of the glucagon receptors. This model has been characterized before and shown to be associated with reduced fasting and prandial glycemia (3). The authors challenged these mice with a high dose of streptozotocin, a beta cell toxin completely destroying beta cell function. Wild type mice became severely diabetic after this challenge with massive hyperglycemia. However, the mice with the glucagon receptor knockout remained in good health with low glucose and had normal glucose tolerance after a glucose challenge, even in the absence of any insulin response.

The study therefore shows that in the presence of glucagon deficiency,

Comments to Bagger et al: Impaired regulation of the incretin effect in patients with type 2 diabetes.

J Clin Endocrinol Metab 96:737-745 (2011)

The incretin effect is defined as the augmented insulin secretion after oral versus intrave-nous glucose administration and is due to the release from the gut of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) after oral glucose; these incretin hormones augment glucose-stimulated insulin secretion (1). The incretin function is of key importance for normal glucose levels after oral glucose. It has also been shown that the incretin effect is impaired in type 2 diabetes (2). This is mainly due to impaired action on insulin secretion by the incretin hormone GIP in type 2 diabetes (3) and a reduced incretin hormone secretion may also contribute in some patients (4).

The new study by Dr Bagger and co-authors presents novel information on the regulation of the incretin function under normal conditions and in type 2 diabetes (5). They challenged healthy volunteers and patients with type 2 diabetes with 25g, 50g and 125g oral glucose. They found in healthy subjects that the incretin effect (defined as the difference in insulin response after oral vs intravenous glucose) was increased by increased glucose and that the increase was such that in spite of the larger glucose challenge at 125g,