Design Principles of Pancreatic Islets: Glucose-dependent Coordination of Hormone Pulses

Pancreatic islets are functional units involved in glucose homeostasis. The multicellular system comprises three main cell types; $\beta$ and $\alpha$ cells reciprocally decrease and increase blood glucose by producing insulin and glucagon pulses, while the role of $\delta$ cells is less clear. Although their spatial organization and the paracrine/autocrine interactions between them have been extensively studied, the functional implications of the design principles are still lacking. In this study, we formulated a mathematical model that integrates the pulsatility of hormone secretion and the interactions and organization of islet cells and examined the effects of different cellular compositions and organizations in mouse and human islets. A common feature of both species was that islet cells produced synchronous hormone pulses under low- and high- glucose conditions, while they produced asynchronous hormone pulses under normal glucose conditions. However, the synchronous coordination of insulin and glucagon pulses at low glucose was more pronounced in human islets that had more $\alpha$ cells. When $\beta$ cells were selectively removed to mimic diabetic conditions, the anti-synchronicity of insulin and glucagon pulses was deteriorated at high glucose, but it could be partially recovered when the re-aggregation of remaining cells was considered. Finally, the third cell type, $\delta$ cells, which introduced additional complexity in the multicellular system, prevented the excessive synchronization of hormone pulses. Our computational study suggests that controllable synchronization is a design principle of pancreatic islets.Comment: 24 pages, 7 figure

Machine learning for the diagnosis of early stage diabetes using temporal glucose profiles

Machine learning shows remarkable success for recognizing patterns in data. Here we apply the machine learning (ML) for the diagnosis of early stage diabetes, which is known as a challenging task in medicine. Blood glucose levels are tightly regulated by two counter-regulatory hormones, insulin and glucagon, and the failure of the glucose homeostasis leads to the common metabolic disease, diabetes mellitus. It is a chronic disease that has a long latent period the complicates detection of the disease at an early stage. The vast majority of diabetics result from that diminished effectiveness of insulin action. The insulin resistance must modify the temporal profile of blood glucose. Thus we propose to use ML to detect the subtle change in the temporal pattern of glucose concentration. Time series data of blood glucose with sufficient resolution is currently unavailable, so we confirm the proposal using synthetic data of glucose profiles produced by a biophysical model that considers the glucose regulation and hormone action. Multi-layered perceptrons, convolutional neural networks, and recurrent neural networks all identified the degree of insulin resistance with high accuracy above $85\%$.Comment: 4 pages, 2 figur

Information flows of diverse autoencoders

The outstanding performance of deep learning in various fields has been a fundamental query, which can be potentially examined using information theory that interprets the learning process as the transmission and compression of information. Information plane analyses of the mutual information between the input-hidden-output layers demonstrated two distinct learning phases of fitting and compression. It is debatable if the compression phase is necessary to generalize the input-output relations extracted from training data. In this study, we investigated this through experiments with various species of autoencoders and evaluated their information processing phase with an accurate kernel-based estimator of mutual information. Given sufficient training data, vanilla autoencoders demonstrated the compression phase, which was amplified after imposing sparsity regularization for hidden activities. However, we found that the compression phase is not universally observed in different species of autoencoders, including variational autoencoders, that have special constraints on network weights or manifold of hidden space. These types of autoencoders exhibited perfect generalization ability for test data without requiring the compression phase. Thus, we conclude that the compression phase is not necessary for generalization in representation learning