Obesity: Multisystem Complications and Insulin Resistance

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Questions and Answers

Which phosphorylation event leads to the dissociation of the p85 subunit of PI3-K from IRS-1?

Tyrosine phosphorylation of IR

Phosphorylation on Ser612 (correct)

Threonine phosphorylation of IRS-1

Phosphorylation on Ser307

What is one consequence of phosphorylation of IRS-1 on Ser307?

Enhanced insulin signaling

Increased tyrosine phosphorylation

Dissociation from the insulin receptor (correct)

Activation of PI3-K

What did transgenic mice with targeted disruption of the IRS-1 gene exhibit?

Increased insulin sensitivity

Improved vascular relaxation

Higher blood pressure and triglyceride levels (correct)

Lower blood pressure than wildtype mice

How do defects in insulin receptor (IR) signaling vary?

They depend on the type of stress and are tissue-specific Signup and view all the answers

What is a mechanism that leads to the inhibition of insulin-stimulated signaling?

Kinase-mediated serine/threonine phosphorylation Signup and view all the answers

What triggers the autophosphorylation of the insulin receptor (IR)?

Binding of insulin to the α subunit Signup and view all the answers

Which enzyme is primarily stimulated by the activation of PI3K?

Serine/threonine kinase Akt Signup and view all the answers

Which of the following factors can lead to insulin resistance?

Defects in receptor structure Signup and view all the answers

How does hyperglycemia contribute to insulin resistance?

By generating reactive oxygen species (ROS) Signup and view all the answers

What is the role of IRS-1 and IRS-2 in insulin signaling?

Interact with PI3K to facilitate downstream signaling Signup and view all the answers

Which statement about the insulin receptor (IR) is incorrect?

It requires glucose binding for activation Signup and view all the answers

What is the primary effect of Akt activation in insulin signaling?

Facilitates glucose transporter translocation Signup and view all the answers

Which of the following elements is not considered an abnormality contributing to insulin resistance?

Enhanced binding of insulin Signup and view all the answers

Which organ system is NOT mentioned as being negatively impacted by obesity?

Skeletal system Signup and view all the answers

What is one of the primary actions of insulin in managing glucose levels?

Inhibition of liver gluconeogenesis Signup and view all the answers

Insulin resistance primarily indicates a reduced action of insulin on which metabolic process?

Glucose metabolism Signup and view all the answers

Which of the following is NOT mentioned as a complication associated with obesity?

Respiratory issues Signup and view all the answers

What effect does insulin have on protein metabolism according to the content?

Inhibits protein breakdown Signup and view all the answers

Which statement about insulin-resistant individuals is correct?

They may show normal insulin action on some non-glucose metabolic pathways. Signup and view all the answers

What is a consequence of insulin's action on adipose tissue?

Induction of lipid storage Signup and view all the answers

Which of the following is an area of ongoing research related to insulin resistance?

Impact on protein turnover and lipid metabolic pathways Signup and view all the answers

What role do the 12 amino acids encoded by exon 11 play in the receptor's function?

They increase the receptor's affinity for IGF-2. Signup and view all the answers

Which receptors are part of the subfamily of receptor tyrosine kinases mentioned?

IGF-1 receptor, insulin receptor, insulin receptor-related receptor. Signup and view all the answers

How do insulin and IGF signaling differ primarily in their biological effects?

Insulin regulates metabolism while IGF regulates growth. Signup and view all the answers

What could hyperinsulinemia in the metabolic syndrome potentially lead to?

Activation of hybrid receptors or IGF receptors. Signup and view all the answers

Which condition is linked with the pathogenesis of acanthosis nigricans?

Insulin resistance. Signup and view all the answers

What effect do changes in IGF binding proteins have on IGF activity?

They alter the IGF activity. Signup and view all the answers

What condition can potentially arise from increased activation of the hybrid receptor?

Increased risk of cancer. Signup and view all the answers

What characteristic feature is commonly observed in individuals with insulin resistance?

Acanthosis nigricans. Signup and view all the answers

What initiates the complex cascade of signaling events in the insulin signaling pathway?

Binding of insulin to the insulin receptor Signup and view all the answers

What are the two main structural components of the insulin receptor?

α-subunit and β-subunit Signup and view all the answers

What occurs to the β-subunits of the insulin receptor upon insulin binding?

They phosphorylate one another and their substrates Signup and view all the answers

Which of the following best describes the role of alternative splicing in the insulin receptor?

It generates heterogeneity in the signaling responses Signup and view all the answers

What is the relationship between the insulin signaling pathway and the IGF-1 signaling pathway?

Cross-talk occurs at certain signaling nodes Signup and view all the answers

Which isoform of the insulin receptor lacks the 12 amino acids encoded by exon 11?

IRᴬ Signup and view all the answers

What type of bonds link the α-subunit and β-subunit of the insulin receptor?

Disulfide bonds Signup and view all the answers

What is the primary function of the tyrosine kinase domain in the insulin receptor?

To phosphorylate substrates Signup and view all the answers

Study Notes

Obesity: Complications

Obesity negatively impacts the development and worsening of complications, affecting virtually all organs and systems.
The current course focuses on insulin resistance and its mechanisms, as it contributes to several obesity-associated complications, including those beyond type 2 diabetes, metabolic syndrome, and cardiovascular events.

Multisystem Complications of Obesity

Figure 2 displays the various organs and systems affected by obesity, highlighting the wide-ranging complications. These include gastrointestinal, endocrinology, cardiology, orthopedics, and more.

Insulin Resistance

Insulin's primary role is regulating nutrient utilization and intermediate metabolism after a meal.
Insulin stimulates glucose uptake in muscles and fat tissue. It also inhibits the liver from producing glucose.
Major insulin actions preserve muscle mass by inhibiting protein breakdown and promoting lipid storage in fat tissues.
In clinical practice, insulin resistance is defined as reduced insulin action on glucose metabolism.

Insulin Signaling Pathway

Insulin triggers a complex chain of signaling events, involving numerous nodes.
The pathway's complexity is significant and not merely linear.
Each node features various isoforms with subtle signal variations.

Insulin Receptor

The insulin receptor binds insulin, initiating a complex cascade of signaling events.
It comprises an alpha subunit (extracellular) and a beta subunit (intracellular with tyrosine kinase domains).
Through its binding, the insulin receptor's beta subunits phosphorylate each other and internal targets. This initiates further downstream signaling via pathways like PI3K. This affects growth, metabolism, and cell division depending on the particular signaling pathway.

Insulin Signaling Pathway: Heterogeneity & Alternative Splicing

The insulin signaling pathway demonstrates considerable complexity and heterogeneity.
Alternative splicing, specifically of exon 11, generates different isoforms of the insulin receptor, with varying affinities for insulin-like growth factor (IGF)-1, one example.

Insulin Resistance: Molecular Mechanisms

Abnormalities in insulin signaling contribute to the condition.
Binding of insulin to the alpha subunit triggers a downstream cascade.
The beta subunit is activated through auto-phosphorylation.
This affects multiple substrates, including insulin receptor substrates (IRS).

Insulin Resistance: Additional Mechanisms

Phosphorylation of IRS-1 can prompt dissociation from downstream effectors, thus inhibiting downstream signaling.
Other mechanisms include degradation of IRS proteins and serine-threonine phosphorylation.
Tissue-specificity and variable response to stress characterize insulin resistance. These involve specific reactive oxygen species during metabolic processes.

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Description

This quiz explores the complications of obesity affecting multiple organs and systems, with a focus on insulin resistance. Understand how obesity contributes to various health issues beyond just metabolic syndrome and cardiovascular complications. Test your knowledge on the physiological roles of insulin and its impact on nutrient metabolism.