While type 1 diabetes causes the destruction of the beta cells of the islets of Langerhans in the pancreas and the development of an absolute insulin deficiency, type 2 diabetes is characterized by insulin resistance and beta cell dysfunction. Before now, researchers knew very little about the concrete pathophysiological processes in the islets of Langerhans during the development of type 2 diabetes. This is primarily because their location in the pancreas means that the islets of Langerhans are not easily accessible.
"Our approach was to examine islets of Langerhans in their natural environment in the pancreas, which means without the isolation process and without the artifacts that possibly accompany it," explains the senior author. Authors used high-resolution mass spectrometry imaging (MALDI imaging) to examine the distribution of metabolic products (cell metabolites) and proteins directly in tissue sections.
"A disrupted balance in the insulin synthesis and insulin release was seen in the mouse model*," adds another author. "This new, previously unknown mechanism leads to beta cell dysfunction as type 2 diabetes progresses."'
Fatty acid esters (stearoylcarnitine) already begin to accumulate at an early stage of type 2 diabetes and prevent insulin synthesis. At the same time, there is also an accumulation of other fatty acids (acetylcarnitine and an accumulation of N-acyl taurines, a group not previously detected in β cells ) that promote the release of insulin. The beta cells consequently no longer have sufficient insulin and their function can no longer be maintained.
Thus, β cell dysfunction results from enhanced insulin secretion combined with an arrest of insulin synthesis.
Mechanism of β cell dysfunction in type 2 diabetes (T2D)
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