Notes on Insulin Resistance, Glucose Transport, and Facilitated Diffusion

Insulin resistance and type 2 diabetes

The cell surface is becoming unresponsive to insulin; it doesn't react to it anymore because it's worn out. This describes or exemplifies type 2 diabetes in simple terms.
The statement highlights insulin resistance as a defining feature of type 2 diabetes.
A quick takeaway: insulin resistance means higher insulin levels are needed to achieve the same cellular response, and the uptake of glucose into cells becomes impaired.

When there are many molecules outside the cell and relatively few inside, random molecular motion (thermal energy) affects how molecules diffuse.
Glucose cannot freely move across the cell membrane on its own due to the membrane’s structure and polarity; it needs a facilitated entry mechanism.
Therefore, glucose transport must be facilitated somehow, either with a pore (channel) or a pump.

Facilitated transport refers to movement of substances across the membrane with the help of transport proteins, moving along the concentration gradient.
In the transcript, glucose access is described as needing a pore or a pump, i.e., a facilitated mechanism.
Pores/channels provide a pathway for specific molecules to diffuse down their concentration gradient.
Pumps can move substances and may require energy input (often ATP) to move substances against their gradient (active transport).

Pore/Channel (facilitated diffusion):
- Movement through a pore or channel down the concentration gradient.
- Does not require direct energy input.
Pump (active transport):
- Movement that can require energy to move a molecule, potentially against its concentration gradient.
- Often uses energy sources such as ATP or electrochemical gradients.

Diffusion: spontaneous movement of molecules from high to low concentration due to random thermal motion.
Facilitated diffusion: diffusion of specific molecules through membrane proteins (pores/channels) down their gradient, without direct energy expenditure.
Active transport: movement of molecules against their gradient, requiring energy input (e.g., ATP) and often a pump protein.
Membrane permeability: the ease with which a molecule crosses the membrane; glucose typically requires a transporter due to limited permeability of the lipid bilayer for polar molecules.

Fick's law of diffusion (net flux): J = -D \, \frac{dC}{dx}
- Where $J$ is the diffusion flux, $D$ is the diffusion coefficient, and $\frac{dC}{dx}$ is the concentration gradient.
Permeability-based view (simplified membrane transport): J = P (C{\text{out}} - C{\text{in}})
- Where $P$ is the permeability of the membrane to the molecule, and $C{\text{out}}$, $C{\text{in}}$ are extracellular and intracellular concentrations.
These equations illustrate why a molecule like glucose requires a facilitated mechanism when its diffusion across the membrane is limited by lipid bilayer properties.

Insulin resistance reduces the effectiveness of insulin signaling, leading to suboptimal glucose uptake into cells, particularly in liver, muscle, and adipose tissues.
The need for facilitated transport of glucose emphasizes the role of transporter proteins (e.g., GLUT family) in physiology and disease, linking cellular transport to whole-body glucose homeostasis.
The dichotomy between pores (facilitated diffusion) and pumps (active transport) helps explain how cells regulate the intake of nutrients when simple diffusion is insufficient.

In many cells, glucose cannot freely diffuse into the cytoplasm; it relies on facilitated transport through membrane proteins.
Insulin resistance (type 2 diabetes) is characterized by reduced cellular responsiveness to insulin, impairing glucose uptake.
Transport across the cell membrane can occur via channels (pores) or pumps, with channels supporting diffusion along a gradient and pumps using energy to move substances, potentially against the gradient.