Loss of mitochondrial adaptation associates with deterioration of mitochondrial turnover and structure in metabolic dysfunction-associated steatotic liver disease.

Background: Obesity and type 2 diabetes frequently have metabolic dysfunction-associated steatotic liver disease (MASLD) including steatohepatitis (MASH). In obesity, the liver may adapt its oxidative capacity, but the role of mitochondrial turnover in MASLD remains uncertain.

Methods: This cross-sectional study compared individuals with class III obesity (n = 8/group) without (control, OBE CON; NAFLD activity score: 0.

Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis.

Impaired proinsulin-to-insulin processing in pancreatic β-cells is a key defective step in both type 1 diabetes and type 2 diabetes (T2D) (refs. ), but the mechanisms involved remain to be defined. Altered metabolism of sphingolipids (SLs) has been linked to development of obesity, type 1 diabetes and T2D (refs.

Deletion of the RabGAP TBC1D1 Leads to Enhanced Insulin Secretion and Fatty Acid Oxidation in Islets From Male Mice.

The Rab guanosine triphosphatase-activating protein (RabGAP) TBC1D1 has been shown to be a key regulator of glucose and lipid metabolism in skeletal muscle. Its function in pancreatic islets, however, is not yet fully understood. Here, we aimed to clarify the specific impact of TBC1D1 on insulin secretion and substrate use in pancreatic islets.

The biomechanical properties of an epithelial tissue determine the location of its vasculature.

An important question is how growing tissues establish a blood vessel network. Here we study vascular network formation in pancreatic islets, endocrine tissues derived from pancreatic epithelium. We find that depletion of integrin-linked kinase (ILK) in the pancreatic epithelial cells of mice results in glucose intolerance due to a loss of the intra-islet vasculature.

DJ-1 Protects Pancreatic Beta Cells from Cytokine- and Streptozotocin-Mediated Cell Death.

A hallmark feature of type 1 and type 2 diabetes mellitus is the progressive dysfunction and loss of insulin-producing pancreatic beta cells, and inflammatory cytokines are known to trigger beta cell death. Here we asked whether the anti-oxidant protein DJ-1 encoded by the Parkinson's disease gene PARK7 protects islet cells from cytokine- and streptozotocin-mediated cell death. Wild type and DJ-1 knockout mice (KO) were treated with multiple low doses of streptozotocin (MLDS) to induce inflammatory beta cell stress and cell death.

Everolimus Stabilizes Podocyte Microtubules via Enhancing TUBB2B and DCDC2 Expression.

Background: Glomerular podocytes are highly differentiated cells that are key components of the kidney filtration units. The podocyte cytoskeleton builds the basis for the dynamic podocyte cytoarchitecture and plays a central role for proper podocyte function. Recent studies implicate that immunosuppressive agents including the mTOR-inhibitor everolimus have a protective role directly on the stability of the podocyte actin cytoskeleton.

Pronounced reduction of cutaneous Langerhans cell density in recently diagnosed type 2 diabetes.

Immune-mediated processes have been implicated in the pathogenesis of diabetic polyneuropathy. Langerhans cells (LCs) are the sole dendritic cell type located in the healthy epidermis and exert tolerogenic immune functions. We aimed to determine whether alterations in cutaneous LC density and intraepidermal nerve fiber density (IENFD) are present in patients with recently diagnosed type 2 diabetes.

The diabetes-prone NZO/Hl strain. Proliferation capacity of beta cells in hyperinsulinemia and hyperglycemia.

New Zealand Obese (NZO) male mice develop a polygenic juvenile-onset obesity and maturity onset hyperinsulinemia. Approximately 50% transit to chronic hyperglycemia. Here we report on the proliferation of beta cells in relation to both the individual's metabolic status and structural parameters of the endocrine pancreas.

The diabetes-prone NZO/Hl strain. II. Pancreatic immunopathology.

We report the first combined light and electron microscopic analysis of the pancreas during the development of type 2 diabetes in the New Zealand Obese (NZO) mouse. As in most other polygenic rodent models of type 2 diabetes, hyperglycemia associated with beta cell destruction is male sex-limited. Increasing degrees of hyperinsulinemia and transition to diabetes were clearly reflected by the islet volume fraction, by the beta cell granulation state, and by ultrastructural changes, primarily of the endoplasmic reticulum.